MICR3320 Exam Study

What is the structure of Flaviviruses?

(+) ssRNA, enveloped virus Flaviviruses are assembled using three viral structural proteins (C, prM and E), a host lipid envelope and the viral genomic RNA. The E protein is a three-domain structure (referred to as domains EDI, E-DII and E-DIII) tethered to the viral membrane and is antigenic determinant

What is the Murray Valley Encephalitis Virus?

(+) ssRNA, enveloped virus Genus Flavivirus, Family Flaviviridae Member of the Japanese encephalitis serogroup MVEV is maintained in enzootic foci in the north of Western Australia and the Top End of the Northern Territory (NT), primarily in a cycle between water birds and Culex annulirostris Spread of MVEV outside enzootic foci is likely due to rainfall and flooding that allowed movement of infected water birds to previously arid environments

What is the West Nile virus?

(+) ssRNA, enveloped virus Genus Flavivirus, Family Flaviviridae Variant circulating in Australia and Papua New Guinea is Kunjin virus West Nile virus cycles between mosquitoes (especially Culex species) and birds. Some infected birds, can develop high levels of the virus in their bloodstream and mosquitoes can become infected by biting these infected birds. After about a week, infected mosquitoes can pass the virus to more birds. Mosquitoes with West Nile virus also bite and infect people, horses and other mammals.

What is Group 2?

(+)ssDNA Enzymes required for replication: - Cellular DdDp - Cellular DdRp RNA can only be synthesized from dsDNA - a complementary DNA has to be synthesised first, to convert genome to dsDNA All replication occurs via cellular DNA-dependent DNA Polymerase - synthesise dsDNA from viral ssDNA genome Newly synthesized viral dsDNA used as template to synthesise - +viral mRNA: translated to viral protein - ss(+) viral DNA genome

What is Group 3?

(+/-) dsRNA Viral dsRNA must be copied to make dsRNA for new virus particle - require RNA-dependent RNA Polymerase Cells do not generally use RdRp Virus particle includes active RdRp that is ready to synthesise vRNA upon infection of host cell vRdRp copies dsRNA genome and also transcribes vmRNA vmRNA translated to viral protein. Replication occurs within the capsid in the cytoplasm, not in the nucleus as for DNA viruses.

What is the Bunyaviruses?

(-) ssRNA, segmented genome, enveloped virus Bunyaviruses are enveloped viruses comprised of only 4 structural proteins. 2 of them are envelope glycoproteins, named Gc and Gn, and the other 2 are internal proteins, the nucleocapsid protein or nucleoprotein (N) and the L protein (the viral RNA polymerase). Most bunyavirus genomes are divided into 3 negative single-stranded RNA segments, which are hidden by multiple copies of N. Genetic reassortment can occur during infection because the RNA is segmented - Reassortment occurs when a cell is infected simultaneously with two different but closely related bunyaviruses.

What is the Crimean Congo haemorrhagic fever virus?

(-) ssRNA, segmented genome, enveloped virus Genus Nairovirus, Family Bunyaviridae Maintained in animal-tick cycle - Hyalomma ticks Transmitted to humans either by close contact with people who are infected; tick bites; contact with infected animals immediately after slaughter - majority of cases occur in people in the livestock industry: vets, slaughterhouse workers Incubation period following tick bite 1-3 days to 9 days ; following contact with blood or tissues 5-6 days to 13 days Acute febrile illness which may be followed by abdominal pain, petechial rash and haemorrhagic phenomena - mortality rate approximately 40%, death occur in the second week of illness

What is the Rift Valley fever virus?

(-) ssRNA, segmented genome, enveloped virus Genus Phlebovirus, Family Bunyavirales Maintained in livestock-mosquito cycle - certain Aedes and Culex species Transmitted to humans by close contact with infected animals immediately after slaughter - majority of cases occur in people in the livestock industry: vets, slaughterhouse workers RVFV has an incubation period of 2-6 days following exposure to the virus Majority of people with RVF have either no symptoms or a mild illness - Typically, patients recover within two days to one week after symptom onset. However, a small percentage (8-10%) of people infected with RVFV develop much more severe symptoms

What are the Mononegavirales group?

(-)ssRNA virus group Includes Rhabdoviridae (eg Rabies virus), Paramyxoviridae (eg Measles virus) After uncoating, the (-) RNA remains associated with nucleocapsid proteins (NPs), other viral proteins (including RdRp) and associated factors needed for RNA synthesis. This complex, including the genome, can be referred to as a viral ribonucleoprotein complex (vRNP) The RdRp becomes active as a transcriptase, using vRNP as template to synthesize viral mRNAs Viral mRNAs have 5' caps and 3' poly-A tails. Process is referred to as primary transcription, uses the infecting genome as template When levels of NP reach a threshold, antigenomes are synthesized and new genomes which are packaged into new virions during maturation

what is the process of virus penetration and uncoating at the plasma membrane?

(A) Entry of a member of the Paramyxoviridae, which bind to cell surface receptors via the HN, H, or G glycoprotein. The fusion protein (F) then catalyzes membrane fusion at the cell surface at neutral pH. The viral nucleocapsid, as RNP, is released into the cytoplasm, where RNA synthesis begins. (B) Model for F-protein-mediated membrane fusion. Binding of HN to the cell receptor (red) induces conformational changes in HN that in turn induce conformational changes in the F protein, moving the fusion peptide from a buried position nearer to the cell membrane

How do viruses spread extracellular and cell-to-cell spread?

(A) Many viruses spread from one host cell to another as extracellular virus particles released from an infected cell. Such extracellular dissemination is necessary to infect another naive host. (B) Some viruses, notably alphaherpesviruses, paramyxoviruses, and some retroviruses, can also spread from cell to cell without passage through the extracellular environment (C) These viruses can therefore be disseminated by both mechanisms

How does Cap-dependent initiation complex compared with picornavirus initiation complex?

(A) Normal initiation of host mRNA involves the eIF4E protein binding to the 5ʹ cap and forming a complex with PABP. Other initiation factors are involved (shown in different colors). The small subunit of the ribosome (40S) is closest to the AUG start codon (B) For initiation of the translation of the picornavirus genome, the host ITAF protein binds to the IRES and substitutes for eIF4E. The IRES is a complex stem-loop structure in the viral 5ʹ UTR. The terminal VPg protein was removed from the 5ʹ end of the genome by a host enzyme. Meanwhile, poliovirus proteolytically degrades eIF4E, thus preventing cap-dependent translation of host mRNA.

What are the Mechanisms of spread by viruses?

(A) The canonical route of virus spread involves the release of completely assembled viral particles to the extracellular environment for subsequent infection of target cells. (B) The formation of syncytia involves the fusion of infected cells with adjacent target cells and remains an important mechanism of direct cell-to-cell spread of viral components. This mechanism of spread has been reported for eg. influenza virus, HIV (C) Intercellular extensions connect two distant cells to facilitate transport of viral components, and their formation requires F-actin polymerization. This mechanism of viral spread has been reported in immortalized lung epithelial cells for eg. influenza virus, respiratory syncytial virus (RSV) (D) Intercellular pores connect two adjacent cells, allowing flow of viral components between infected cells and target cells. This mechanism of spread was described for measles virus in human airway epithelial cells.

What is Group 1?

+/- dsDNA Enzymes required: - DNA-dependent DNA Polymerase DdDp - DNA-dependent RNA Polymerase DdRp Small viruses use cellular DNA Pol Larger viruses encode their own DNA Pol Some viruses encode their own DdRp Viral dsDNA synthesized with DdDp Viral mRNA synthesized with DdRp - viral protein translated Examples: Herpesvirus, Papillomavirus, Polymavirus

What is Antiretroviral Therapy for HIV Infection?

- Nucleoside reverse transcriptase inhibitors (NRTIs) - Non-nucleoside reverse transcriptase inhibitors (NNRTIs) - Protease inhibitors (Pis)) - Integrase inhibitors (INSTIs) - Entry inhibitors: Fusion inhibitors (FIs) - Entry inhibitors: Chemokine receptor antagonists (CCR5 antagonists) - Entry inhibitors: (CD4-directed post-attachment inhibitors)

What are the Molecular events during each stage of the virus replication cycle

1. Attachment: The virion attaches to the host cell, via its receptor(s). 2. Penetration and uncoating: The virion's genome enters the host cell. 3. Synthesis of early proteins: The proteins expressed early in an infection often have one of three functions: to shut down the synthesis of host proteins, to regulate expression of viral genes, or to synthesize viral nucleic acids. 4. Synthesis of new viral genomes and late proteins: regulatory events that cause a shift from synthesis of early mRNA to the making of new genomes. - Late proteins are those expressed after genome replication has begun. - The proteins made at this phase are usually structural proteins, meaning that they will become components of the progeny virions. - In some viruses, with small genomes, Stages 3 & 4 overlap. 5. Assembly: This is the stage when the component parts of the virion assemble into completed virions. 6. Release: This stage, the release of the newly assembled viruses, is the last step. Shedding of viruses from animal cells can be gradual and may not lyse the host cells immediately.

What is the Influenza virus replication cycle?

1. The virus attaches to its receptor (sialic acids (SA, N-acetylneuraminic acid) on the surface of the host cell. 2. The virus is internalized by endocytosis during the penetration step. 3. During uncoating, the (ss -RNA) genome segments and associated proteins (vRNPs) are released into the cytoplasm, where they are transported to the nucleus. 5. The influenza genome is copied to make a double-stranded template, that can be used for production of mRNA and new genomes. 6. The mRNAs are exported to the cytoplasm and translated to make IV proteins. 7. Some influenza proteins reenter the nucleus to assemble with new genome segments, whereas others assemble at sites of future budding. 8. The vRNPs assemble with other component parts of the virus. The virus exits the host cell through budding, assisted by a viral enzyme (the neuraminidase, NA) that degrades the host surface sugars (sialic acids (SA, N-acetylneuraminic acid) that would otherwise tether the virus to the cell surface

What was the divergence of nCoV?

2019-nCoV sufficiently divergent from SARS-CoV to be considered a new human-infecting betacoronavirus - 2019-nCoV genomes >99.98% identical - 88% identity to two bat SARS-like CoV collected Zhoushan 2018 - 79% identical to SARS-CoV - 50% identical to MERS-CoV

Where did the novel COVID-19 emerg?

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How is complement stimulated by antibodies?

A cell infected by an enveloped virus has virus spikes on the surface of its plasma membrane. Antibodies that bind to these spike proteins stimulate the complement system so that the MAC (membrane attack complex), forms on the infected cell. The infected cell dies before viral replication is complete. Viruses may evade the complement response. - Influenza virus: the M1 viral matrix protein prevents the first complement activation step from occurring. - herpes simplex virus I and smallpox virus make proteins that interfere with the third step. In all of these evasion strategies, MAC formation is prevented.

What is the model for HIV-1 Transmission

A genetically and phenotypically diverse quasi-species of virus is present in the semen, cervicovaginal secretions, or blood of persons with chronic HIV-1 infection, but most often, only a single virion or virally infected cell is transmitted and leads to productive clinical infection. Other viruses may breach the mucosal or cutaneous surfaces, but they generally do not result in productive infection or contribute to it, presumably because such viruses are defective or less fit or simply fail to come into contact with susceptible target cells. R0 represents the basic reproductive ratio, which corresponds to the number of secondary infections caused by one infected cell. If this number falls below 1, infection is extinguished. In acute infection, the number of productively infected cells and the concentration of free virus in the plasma increase exponentially, with an estimated R0 of 8

What are the requirements for a successful infection?

A susceptible cell has a functional receptor for a given virus - the cell may or may not be able to support viral replication A resistant cell has no receptor - it may or may not be competent to support viral replication A permissive cell has the capacity to replicate virus - it may or may not be susceptible A susceptible and permissive cell is the only cell that can take up a virus particle and replicate it - Dose - enough virus - Access to target cells: susceptible, permissive - Absent or insufficient host immunity

What is the SINV transcription of genomic & subgenomic RNA?

A. Full-length (+) strands, with 5' cap and 3' polyA tail (genomic RNA, gRNA) B. Full-length (-) antigenomes (light green) that are part of the double-stranded replicative form (RF) C. Subgenomic (+) RNA (sgRNA) with a 5' methylated cap, 3' poly-A tail, encoding the structural polyprotein.

What is the AIDS defining criteria

AIDS: presence of HIV infection and either a CD4+ T cell count of <200 cells per μl or an AIDS-defining complication AIDS-defining conditions Candidiasis of bronchi, trachea, oesophagus, or lungs Cytomegalovirus diseases (particularly retinitis) (CMV) Kaposi's sarcoma (KSͿ (HHV-8) Tuberculosis (TB) Pneumocystis jirovecii pneumonia Toxoplasmosis of brain

What is the emergence of a new clinical syndrome associated with immunodeficiency and with an infectious etiology?

Acquired immune deficiency syndrome (AIDS) is the end stage disease caused by infection with human immunodeficiency virus (HIV) First recognised as a clinical entity in 1981: Pneumocystis pneumonia, Kaposi͛s sarcoma and Pneumocystis pneumonia among homosexual men A Cluster of Kaposi͛s Sarcoma and Pneumocystis carinii pneumonia among homosexual male residents of Los Angeles and range Counties, Investigations suggested the possibility of a cellular-immune dysfunction related to a common exposure, that predisposed individuals to opportunistic infections such as pneumocystis and candidiasis

How do Adjuvants work by

Acting as an antigen depot, releasing it slowly Inducing an inflammatory repsponse that enhances the host immune response to the vaccine antigen

What do activated CTL use?

Activated CTLs use the CD8 surface molecule and the TCR to bind to MHC-I molecules displaying epitopes on their surface If the endogenous epitope is recognized as foreign, the CTL kills the infected cell.

What is the viral CNS infection, AFP/AFM?

Acute flaccid paralysis: acute onset of flaccid paralysis in one or more limbs May be caused by anterior horn cell infection with wild or vaccine polio virus, or other viruses - e.g. Enterovirus 71 Anterior horn of spinal cord contains bodies of motor neurons, which puts brain's decisions - based on sensory information -into action. Damage to anterior horn cells affects muscle movements

How are Acute infections present, common publich health problems

Acute infections are often associated with serious epidemics affecting millions of people Infected host is often infectious before symptoms manifest By the time the host is sick enough to stay home ('social isolation'), away from susceptible potential new hosts, transmission has already occurred Such infections are very difficult to control in large populations or crowded environments (eg. Nursing homes, daycare centres, schools, offices) Effective antiviral therapy requires treatment early in infection - most often initiated too late in disease course

What are acute infections?

Acute infections are rapid and self-limiting Rapid onset of disease with a short but occasionally severe course Disease symptoms tend to resolve over a period of days Rapid production of infectious virions, followed by resolution and elimination of the infection by a healthy host ("clearance") Only occur when intrinsic and innate immune responses are transiently bypassed

How does Adenovirus uncoat and deliver viral genoms into nucleus

Adenoviruses have naked virions with prominent spikes, enclosing a linear dsDNA genome that must enter the nucleus for expression and replication. After attachment, adenovirus is internalized through clathrin-coated pits and enters the endosome system. The virus spike proteins dissociate from the rest of the capsid early after internalization. Acidification of the late endosome releases several proteins including protein VI, which is cleaved by a viral protease activated by the chemical conditions in the maturing endosome. Protein VI ultimately causes lysis of the endosomal membrane and the release of the partially disassembled adenovirus capsid into the cytoplasm. In an extended penetration and uncoating stage that can last 40-60 min, the capsid moves along the microtubule cytoskeleton, ultimately reaching a nuclear pore complex. Docking with the nuclear pore complex causes conformational changes in both the capsid and the nuclear pore complex, which together result in the release of virus DNA into the nucleoplasm.

What are the different viral components are synthesised during an infection?

After the virus attaches to its host cell, the viral genome enters the cell and the eclipse phase begins. The cell fills with viral mRNA; cellular mRNA synthesis may completely shut off within just a few minutes. As viral mRNA increases, so do the levels of viral proteins needed for gene expression and genome replication. Next, viral genomes begin to accumulate and the capsomeres are synthesized. Finally, just before lysis, the cell fills with intracellular virions which have assembled from their component parts.

What is the Picornaviridae VRCs process?

After uncoating, the IRES(Internal ribosome entry site) enables the genome to be translated (1), making a polyprotein that is processed into individual proteins (2). The proteins form VRCs (3) in which doublestranded replicative forms are used to make mRNA and new genomes (4) that are ultimately used to make new virions

What are the key ideas for (+)ssRNA viruses?

All RNA genome viruses must encode an RNA-dependent RNA polymerase (RdRp). No hostderived enzyme is capable of synthesizing complimentary RNA from an RNA template (+) ssRNA viruses replicate in a virus replication complex (VRC) - composed of viral and host proteins, and host lipids. Escape recognition of dsRNA intermediates by host innate immune responses. (+) ssRNA virus genomes are translated immediately upon uncoating and one of the first proteins translated is RdRp. Picornaviruses lack a 5' cap and utilise a VPg protein and IRES within the 5' UTR to initiate translation Flaviviruses encode a single, long polyprotein that can be post-translationally cleaves to produce individual proteins (structural and non-structural Suppression of translation termination, programmed ribosome frameshift are examples of strategies used by (+)ssRNA viruses to encode multiple proteins within overlapping sequences

What must all RNA viruses encode?

All RNA viruses must encode either an RNA-dependent RNA polymerase or a reverse transcriptase for efficient replication RNA-dependent RNA polymerase and reverse transcriptase lack proofreading activity and contribute to viral diversity

How do viruses subvert or co-opt the misfolded protein response triggered in the endoplasmic reticulum?

All enveloped viruses synthesize transmembrane proteins using ribosomes docked to the rough endoplasmic reticulum (ER) - the volume of viral translation can lead to misfolding or delayed folding of proteins in the ER Other viruses use ER membranes in their virus replication compartments, which also blocks normal ER function The result is that the cell triggers an ER stress response called the unfolded protein response to restore ER homeostasis A normal unfolded protein response results in three subpathways that trigger (1) a slowdown of translation, which allows for more time for proteins to fold; (2) an increase of the ER folding capacity by increasing the number of chaperones in the ER lumen; and (3) increased degradation of unfolded and misfolded proteins. A prolonged, ineffective unfolded protein response can lead to apoptosis

What ways can viruses introduce genomes into nuclease

All eukaryotic RNA viruses except orthomyxoviruses (influenza) and retroviruses (HIV) express and replicate their genomes in the cytoplasm Alll eukaryotic DNA viruses except poxviruses (vaccinia and variola) express and replicate their genomes in the nucleus

What are the origins of diversity in RNA virus genomes - misincorporation of nucleotides

All nucleic acid polymerases insert incorrect nucleotides during chain elongation. DNA-directed DNA polymerases have proofreading capabilities in the form of exonuclease activities that can correct such mistakes RNA-dependent RNA polymerases do not possess this capability. frequency of errors in DNA replication is about 10,000-fold lower compared to RNA replication. polymerization errors cause lethal amino acid changes, while other mutations may appear in the genomes of infectious virus particles. Nidovirales allows faithful replication of the large (up to 32 kb) RNA genomes. The RNA synthesis machinery includes proteins not found in other RNA viruses, such as ExoN, a 3ʹ -5ʹ exonuclease. ExoN provides a proofreading function for the viral RNA polymerase

What Accessory Proteins do all retroviruses, HIV have

All retroviruses express five non-enzymatic structural subunits: - SU - the surface protein for receptor binding - TM - the transmembrane protein found in the viral envelope - MA - the matrix protein, between the capsid and envelope - CA - the capsomer - NC - the nucleoprotein, associated with the RNA genome TM and SU form the Env viral spike, needed for attachment and penetration. All retroviruses encode three enzymes: reverse transcriptase, integrase and protease

What are all the major structural proteins for HIV-1 virions synthesised as

All the major structural proteins that form the internal parts of the HIV-1 virion are synthesized as polyproteins The Gag and Gag-Pol polyproteins give rise to proteins MA, CA, NC, p6, protease, reverses transcriptase, and integrase after proteolysis

What is the Alphaviruses geographical distribution?

Alphaviruses are subdivided into those associated with polyarthritis and rash (predominantly Old World strains) and those associated with meningoencephalitis (predominantly New World strains). Old World group strains include CHIKV, o'nyong nyong virus (Central Africa, similar to CHIKV), Ross River and Barmah Forest viruses (Australia and the Pacific), Sindbis virus (cosmopolitan), and Mayaro virus (South America).

What are licensed adjuvants?

Alum (aluminum hydroxide or phosphate), HBV vaccine Monophosphoryl lipid A (isolated from surface of bacteria; TLR-4 ligand), in HPV MF59 (squalene oil-in water emulsion; antigen depot), Influenza vaccine

What is the process of viral entry through Caveole

An alternative form of entry that does not involve clathrin After internalization, the virus traffics through the caveosome and from there to the endoplasmic reticulum Other endocytic caveolar vesicles may instead fuse with an early endosome Vesicles formed by caveolin require a protein called dynamin and do not always become endosomes or fuse with the lysosome. Viruses that enter by the caveolin route are not exposed to low pH but are consequently exposed to the resident proteins in the endoplasmic reticulum, such as the Hsp105 protein found exclusively in the membrane of the endoplasmic reticulum. These endoplasmic reticulum proteins are needed for uncoating, comparable to the need for low pH for viruses that enter through receptor-mediated endocytosis.

How do some viruses use membrane fusion with the outside surface of the cell for penetration

An enveloped virion is covered by a protein-rich lipid bilayer derived from its former host and contains proteins of both host and viral origin. Penetration and uncoating by enveloped viruses necessarily includes fusion of the virion envelope with a host cell membrane. Fusion can be defined as the two lipid bilayers becoming a single lipid bilayer. In the case of enveloped viruses a component of one of the virus spike proteins, termed the fusion protein, has a region termed the fusion peptide that becomes catalytically active following irreversible attachment. The blue lipid bilayer fuses with the orange lipid bilayer, catalyzed by a protein complex containing a fusion peptide. Soon after fusion the phospholipids (blue and orange) from both bilayers will mix.

How do Antibodies help control a viral infection?

Antibodies flood the lymphatic and circulatory systems - when they encounter virions, they bind to epitopes on the virion surface Many antibodies can bind to the surface of the virion at the same time, which may have the effect of neutralizing the virion A neutralized virion can no longer bind to its normal receptor on a host cell because the large antibodies surrounding it physically occlude the viral spike proteins and prevent them from reaching their receptors. The constant region of the neutralizing antibodies can be bound by phagocytes such as macrophages - a process known as opsonization - which subsequently engulf the coated virions and degrades them (A) When a neutralizing antibody binds to a virion, the antibodies physically prevent the virion from approaching its receptor (B) Opsonization Professional APCs use a cellular receptor that binds to the constant region of antibodies to initiate phagocytose and destroy a virus.

How is Secretory antibody, IgA, critical for antiviral defense at mucosal surfaces?

Antibody-producing B cells (plasma cells) in the lamina propria of a mucous membrane secrete the IgA antibody - also called polymeric IgA [pIgA]. pIgA is a dimer, joined at its Fc ends. For IgA to be effective in defense, it must be moved to the surface of the epithelial cells that line body cavities. This process is called transcytosis. A virus particle infecting an epithelial cell potentially can be bound by internal IgA if virus components intersect with the IgA in the lumen of vesicles during transcytosis. This process is likely to occur for enveloped viruses, as their membrane proteins are processed in many of the same compartments as those mediating transcytosis.

What occurs when Influenza virus A undergoes reassortment?

Antigenic shift If cell is infected with 2 different influenza viruses, the RNAs of both viruses are copied in the nucleus. When new virus particles are assembled at the plasma membrane, each of the 8 RNA segments may originate from either infecting virus. The progeny that inherit RNAs from both parents are called reassortants.

How do Viruses affect host cell apoptosis?

Apoptosis is a form of programmed cell death outcome is protection of the entire organism of which it is a part, or to accomplish tissue biogenesis during development - Can cause CPE common response to viral infection - minimize the number of infectious virions produced and thereby help protect the entire organism from the virus Several signal transduction cascades can trigger apoptosis in uninfected cells These pathways culminate in activation of the enzyme caspase 3, a protease that subsequently triggers cell death with the features characteristic of apoptosis: condensed chromatin, fragmentation of DNA, and cell shrinkage and blebbing to produce apoptotic bodies that are easily degraded by phagocytic immune cells

How can Ribosomal frameshifts be a result of multiple proteins being encoded using overlapping RNA sequences?

Approximately 15% of the time, the pseudoknot causes the ribosome to pause during translation elongation. During a programmed -1 frameshift, a slippery sequence such as UUUUUUA has an A that is used twice, once as the last nucleotide of a codon (UUA) and a second time as the first nt of the next codon (AGU). The ribosome is stalled on the slippery sequence by the pseudoknot structure in 3'. In about 10% cases, the ribosome will backtrack one nucleotide, creating one or more mismatchs between tRNAs and mRNA Translation resolves on the backtracked ribosome in the -1 frame

How do Viruses assemble from a polyprotein precursor

Assembly from a polyprotein precursor, illustrated with the poliovirus polyprotein that contains the four proteins that form the heteromeric structural unit. These proteins are synthesized as part of the single polyprotein precursor from which all viral proteins are produced by proteolytic processing including the viral-encoded protease. For simplicity, only the P1 capsid protein precursor and its cleavage by the viral protease 3CD are shown.

What is an example of a scaffolding protein use?

Assembly of herpes simplex virus 1 nucleocapsid requires the scaffolding protein pre-VP22a HSV-1 VP22a is the major component of interior core present in assembling nucleocapsids, forms scaffold-like structures Self-association of pre-VP22a stimulates binding to VP5, the protein that forms structural units of capsid V5 interaction with scaffolding protein guides and regulates VP5 self-assembly Omission of the scaffolding leads to production of partial and deformed nucleocapsid shells Once nucleocapsids have assembled, scaffolding proteins must be discarded, so that viral genomes can be accommodated The virion protease VP24 is essential for DNA encapsidation. This protein is incorporated into the assembling nucleocapsid as a precursor VP24 cleaves the scaffolding protein to remove a short C-terminal sequence that is required for binding to VP5, to disengage scaffolding from structural proteins, once assembly of the nucleocapsid is complete. The VP24 protease also degrades the scaffolding protein so that encapsidation of the genome can begin.

How does Assembly within the nuclease occur

Assembly of the majority of viruses with DNA genomes, including adenoviruses, papillomaviruses, and polyomaviruses, takes place within infected cell nuclei, the site of viral DNA synthesis. Viral proteins destined for the nucleus are synthesized by cytoplasmic polyribosomes, as illustrated for the influenza virus NP protein. They engage with the cytoplasmic face of the nuclear pore complex and are translocated into the nucleus by the protein import machinery of the host cell. Some viral structural proteins enter the nucleus as preassembled structural units, as shown for - polyomavirus [Py] VP1 pentamers associated with one molecule of either VP2 or VP3, and - adenovirus hexon trimers formed with the assistance of the viral L4 100-kDa protein chaperone.

How do Viruses assemble though a Chaperone-assisted assembly

Assisted assembly. Some structural units are assembled only with the assistance of viral chaperones, such as the adenoviral L4 100-kDa protein, which is required for formation of the hexon trimer from the protein II monomer.

What is the Chronic hepatitis B management?

Based on the levels of serum HBV DNA, ALT and severity of liver disease Nucleoside or nucleotide analogues (NUCs) - e.g. Lamivudine inhibits HBV DNA synthesis → suppression of viral replication and reduction of hepatic necrosis, and HBeAg seroconversion Antiretroviral treatment can select for drug resistant virus - Approximately 70% of patients after 5 years on lamivudine have resistant HBV

How do bats play a role in animal-to-human transmission?

Bats are natural reservoirs that can sustain many viruses that are extremely pathogenic to humans, including Nipah, Hendra, rabies, Ebola, and SARS coronaviruses, with no visible sign of disease Significant differences between bat and human immune responses - eg. The Type I Interferon IFN-alpha, a major innate anti-viral immune response, is constantly active in bats. In humans this response is only activated when a virus infection is detected In humans this persistent activation would induce immunopathology; in bats the inflammatory response is down-modulated

What is the assembly of a retrovirus from polyprotein precursors?

Because multiple ribosomes translate the Env RNA, SU and TM arrive at the plasma membrane in patches The Gag polyprotein of all retroviruses contains the MA, CA, and NC proteins linked by spacer peptides. About 10% of Gag translation products carry the retroviral enzymes, denoted by PR, RT, and IN, at their C termini Association of Gag molecules with the plasma membrane, with one another, and with the RNA genome via binding of NC segments - initiates assembly at the inner surface of the plasma membrane (1) MA segment may bind specifically to the internal cytoplasmic domain of the TM-SU glycoprotein. Assembly of the particle continues by incorporation of additional molecules of Gag (2) Fusion of the membrane around the budding particle releases the immature noninfectious particle (3) Cleavage of Gag and Gag-Pol polyproteins by the viral protease (PR) produces infectious particles with a morphologically distinct core (4)

What is a benign tumour?

Benign: abnormal growth restricted to one site

How does viral fusion occur with Influneza virus?

Binding to a receptor (1) or a change in pH causes a rearrangement in the viral spike protein, revealing the fusion peptide (2), which is an α-helix with a hydrophobic surface that can penetrate host membrane lipids (3). The viral fusion peptide causes scission of the cell membrane (4), draws the viral envelope into close apposition with the host cell membrane (5), creates a hemifusion structure (6), and then catalyzes pore formation (7) so that the viral contents enter the cytoplasm

What is Francis Crick central dogma of molecular?

DNA —> RNA —> protein

What forms do viral genomes exist in?

DNA, RNA or DNA with short segments of RNA Double stranded, single stranded (+) strand, (-) strand, or ambisense Linear, circular, segmented, continuous, gapped

What is Chronic obstructive pulmonary disease (COPD)?

Develops as a significant and chronic inflammatory response to inhaled irritants (e.g. smoking) - narrowing of the airways and scaring

What are Diploid retroviral genome?

Diploid RNA genome (both copies are identical) Bound to tRNA - serves as primer for reverse transcription - bound to viral RNA at the primer binding site (PBS) Each RNA copy is bound together in a kissing loop complex through complementary binding of sequences in the sl1 loop of the 5' region

How is the H5N1 influenza virus and example of cross-species transmission?

Direct transfer of a virulent avian H5N1 virus to humans was first documented in 1997 Birds infected with avian influenza viruses generally experience no overt pathogenesis. While virulent mutants do arise occasionally, These properties indicate that influenza virus is in evolutionary stasis in birds The avian hosts provide the stable reservoir for influenza virus gene sequences that emerge as recombinants capable of transspecies infection

What is polarized release of viruses from cells?

Directional release of virus from polarized cells at a mucosal surface permits avoidance of local host immune response, and facilitates spread within the body Viruses released at the apical surface establish localized infection: underlying lymphatic and circulatory vessels rarely invaded Viruses released at basolateral surface of polarized epithelial cellls are distant from defenses of the lumenal surface and can access underlying tissues, and facilitate systemic spread

What is the Reemergence of wild type HIV after ceasing antiretroviral therapy?

Discontinuation of the antiretroviral therapy regimen will remove the selective pressure on HIV Reversion to wild type virus WT virus may have greater replicative fitness than mutant , drug resistant virus Growth of WT virus may outpace resistant virus - reemergence of a largely WT population

What is Human metapneumovirus?

Discovered in 2001, HPMV is in paramyxovirus family along with respiratory syncytial virus (RSV) Common symptoms include cough, fever, nasal congestion, shortness of breath - may progress to bronchitis or pneumonia; exacerbates COPD; associated with rare neurological complications including encephalitis Infectious virus is shed for 7-9 days following infection - viral clearance is linked to development of adaptive immunity HMPV causes upper and lower respiratory tract infections in people of all ages - especially among young children, older adults and immunocompromised Second most common cause of bronchiolitis in children (after RSV)

What is disease and virulence?

Disease is a harmful pathologic consequence of infection. In many cases, infection is apparently harmless to the host and does not cause disease (= asymptomatic or inapparent infection) Most viruses establish infection in a larger number of hosts than they cause disease; - viruses like Ebola, HIV, and rabies are the exception The virus-associated disease may be defined as a series of non-specific symptoms or signs (eg. Fever, malaise, anorexia) or they may provide important clues as to the nature of the pathogenic process (eg. hepatitis, immunodeficiency, paralysis) Virulence is the relative capacity of a virus to cause disease: - virulent viruses cause disease in greater proportions of infected hosts, and cause more severe disease, than viruses of lower virulence

What are the Chikungunya virus lineages?

Distribution of CHIKV lineages that are associated with recent outbreaks around the world before and after year 2000 Disease first emerged in Tanzania in 1952 and prior 2004 transmission was largely restricted to Africa

What animals maintain Middle East Respiratory Syndrome (MERS)?

Dromedary camels are reservoir host; transmission to humans has been demonstrated Thought to have originated in bats

What is the SARS-CoV-2 Genome Organization, Subgenomic mRNAs, and the Virion Structure?

Each viral transcript has a 5′-cap structure and a 3′ poly(A) tail). Upon cell entry, the genomic RNA is translated to produce nonstructural proteins (nsps) from two open reading frames (ORFs), ORF1a and ORF1b. Proteolytic cleavage of the polyproteins is mediated by viral proteases Viral RdRp (nsp12) transcribes (-)sense RNA that serves as template for synthesis of (+) sense genomic RNA (gRNA), and subgenomic RNAs (sgRNA) gRNA is packaged with assemblying virion sgRNA encode spike (S), envelope (E), membrane (M), nucleocapsid (N) and several accessory proteins

What are the SV40 early and late transcript?

Early transcription proceeds unidirectionally terminating approximately halfway around the circular genome Alternative splicing is the major mechanism by which SV40 encodes so many different proteins using a small amount of DNA, resulting in three different mature early mRNAs that encode either small t antigen, large T antigen, or the 17-kT protein A. Map of early transcripts. Each mRNA is represented by a green line. Thin black lines connect exons. B. Map of late and very late transcripts. Each mRNA is represented by a green line. Thin black lines connect exons. The miRNA is a small regulatory RNA that is expressed late during infection

What are the Orthomyxoviridae group, Influenza virus?

Eight genome segments, each bound to NP and to proteins PA, PB1 and PB2. The 3' and 5' ends contain secondary structures. The most abundant proteins in the influenza virion are encoded by dedicated mRNA, most proteins are encoded by overlapping sequences For example, PB1-Fb2 is synthesized from the single PB1 mRNA, after programmed +1 ribosomal frameshift For viruses of the Orthomyxoviridae family, including influenza, transcription takes place in the nucleus, not the cytoplasm

What is the viral CNS infection, Encephalitis?

Encephalitis: infection (inflammation) of the brain - Myelitis: inflammation of the spinal cord; when both brain and spinal cord are involved, condition is called encephalomyelitis - Encephalitis with meningitis is called meningoencephalitis Symptoms: headache, fever, confusion, drowsiness; more advanced disease includes convulsions, seizures, hallucinations, memory loss and coma; can be fatal Viral encephalitis may be direct effect of acute infection or a complication of latent disease Most diagnosed viral encephalitis is caused by enterovirus; HSV; rabies virus and arboviruses

What are the CNS, Connective Tissue, and Skeletal and Cardiac Muscle characterised as?

Endothelial cells are backed by a dense basement membrane In the CNS the basement membrane is the foundation of the blood-brain barrier (a selective permeability system) Viruses may pass through capillary endothelium directly and enter stroma of choroid plexus, then cross epithelium into CSP > infect brain tissue May also cross BBB in cells, via transcytosis

What is the Rhinovirus?

Enterovirus genus of Picornaviridae family Transmitted by droplets and fomites >150 serotypes known - many strains circulate at once, with seasonal peaks; causes 50% of common cold illnesses Optimal temperature for replication is 33 deg C, temperature in the nasopharynx - upper respiratory tract infection Causes more serious illness: exacerbation of wheezing and asthma in young children; otitis media; sinusitis; chronic bronchitis

Where does HIV entry occur?

Entry of HIV occurs largely across mucosal surfaces Myeloid DCs, plasmacytoid DCs and Langerhans cells are all susceptible to infection with HIV DCs express high levels of C-type lectins, including DC-specific intercellular adhesion molecule 3 (ICAM3)-grabbing non-integrin (DC-SIGN) DC-SIGN glycoproteins are the main HIV attachment factors at the surface of dermal and mucosal DCs HIV transmission can occur across the infectious synapse, exocytic pathway and de novo virus production R5 variants make up the majority of transmitted and founder viruses

What is Haematogenous Spread?

Entry of viruses into bloodstream often results in disseminated infection Viruses may enter blood directly through capillaries; by replicating in endothelial cells; or by inoculation by a vector bite Virus replicates at entry site and is released into extracellular fluid, which can be taken up by local lymphatic vascular system Lymphatic vessels drain into circulatory system > viruses enter bloodstream In the lymphatic system viruses pass through LN where they encounter migratory immune cells > infected immune cells release virus into plasma or tissues

What are the classes of virions

Enveloped virions, have a lipid bilayer (D) naked virions, do not (A)

What shapes can enveloped viruses have?

Enveloped viruses may either be helical or icosahedral nucleocapsids

What are Hepadnaviruses, Hepatitus B Virus?

Enveloped viruses, have circular genomes (3.3kb) with both DNA and RNA in an unusual arrangement! - Double stranded DNA, with a gap of single stranded DNA - The longer DNA strand has a terminal protein (P) attached at 5' end - Shorter DNA is a DNA-RNA chimera, small number of RNA nts at 5' end Triplex DNA region Use reverse transcription to amplify their genomes, even though their genomes are predominantly DNA

What is the Retroviridae?

Enveloped, (+) ssRNA genomes. Use RT to synthesize cDNA intermediate - HIV Retroviral elements can exist in the human (an other mammals) genomes in two forms: Endogenous: common in the genomes of humans (4-8%) - ancient relics of germ line infection. Exogenous: Horizontally transmitted infectious viruses (eg HIV) that integrate dsDNA, complimentary to their genome, into a host chromosome for gene expression

What is the Parainfluenza virus?

Enveloped, (-) sense ssRNA genome Paramyxoviridae (Respirovirus and Rubulavirus) Contain haemagglutinin and neuraminidase Transmission and pathology similar to influenza viruses, but there are difference: Lower rates of mutation: - little antigenic drift, - no antigenic shift Leading cause of croup in young children Can cause serious disease in infants and small children - Only transitory immunity to reinfection; infection becomes milder as child ages

What is Rabies?

Enveloped, (-) ssRNA, bullet-shaped virus Rhabdoviridae (Lyssavirus) Spread by bite from infected animal; salivary contamination of mucous membranes; aerosols Virus replicates first in muscle, moves along peripheral nerves to CNS via retrograde flow in axons -typically via sensory and motor nerves at the initial site of infection Once virus enters the nerves it is not accessible to the host immune defences Infection cycle completed when virus replicates in the salivary glands

What is Varicella Zoster Virus (VZV)?

Enveloped, dsDNA genome - Herpesviridae Varicella (chickenpox) following primary infection - self-limiting disease of children; morbidity and mortality in other age groups and immunocompromised Herpes zoster (shingles) following reactivation of VZV in sensory nerve ganglia - most often in the elderly or immunocompromised Encephalitis in immunocompromised patients

What is the HIV genome and virion?

Enveloped, ss (+) RNA virus with a DNA intermediate, which replicates using a viral RNA-dependent DNA polymerase: reverse transcriptase (RT) The 2 copies of ss RNA codes for structural (Gag, Pol, and Env), regulatory (Tat and Rev), and accessory proteins (Vpu, Vpr, Vif, and Nef)

What is influenza?

Enveloped; ss(-) sense RNA segmented genome Orthomyxoviridae family - 3 genera: IVA, IVB, IVC

What is Hantavirus Pulmonary Syndrome (HPS)?

Enveloped; ssRNA(-), segmented Family Bunyaviridae (Hantavirus) HPS is a severe, often fatal (~40% fatality rate), respiratory disease caused by infection with a hantavirus Flu-like illness (muscle aches, fever, fatigue) progressing to coughing, dyspnoea, respiratory distress, pulmonary oedema and cardiovascular collapse HPS first recognised in 1993 outbreak in the Four Corners region of SW United States - unusual illness struck a Navajo tribe living on the border of new Mexico and Arizona Originally named 'Four Corners Disease', since named 'Sin Nombre virus' Reservoir host was identified as deer mouse (Peromyscus maniculatis) 150,000 to 200,000 cases of hantavirus disease occur per year, of which 70% to 90% correspond to HFRS cases in China

What is the Error Threshold?

Error threshold: a mathematical parameter that measures the complexity of the information that must be maintained to ensure survival of the population Too much mutation can lead to loss of vital information, while too little mutation can lead to host defenses overcoming the virus Mutation is balanced by selection and survival If error threshold is exceeded: infectivity is lost If below error threshold: cannot produce enough mutations to survive selection The greatest fitness is when mutation rates approach the error threshold RNA viruses evolve close to their error threshold DNA viruses evolve far below their error threshold

What is the evolving host-virus interaction?

Evolving virus-host interactions are unstable and unpredictable Selective forces are applied to both host and virus, and are magnified when host populations are small Virus in a stable relationship may acquire a new property that increases its virulence or spread - the virus-host relationship is no longer stable Introduction of a virus in a new geographic location is characterised by evolving host-virus interactions I - e.g attempt to use myxoma virus infection to rid Australia of rabbits

How do viral gene expression and genome replication take advantage of host cell transcription, translation & replication features?

Expression of viral regulatory proteins and enzymes results from an interaction between viral nucleic acids, proteins, and the host transcription and translation systems. Bacterial and eukaryotic mRNA molecules have quite different structural features which are required for proper translocation, translation, and stability. These features impact virus gene expression strategies, examples: - transcription from a DNA template occurs in the cytoplasm in the Bacteria, but in the nucleus in the Eukarya. - mRNA of bacteria has internal ribosome-binding sites, also known as Shine-Dalgarno sequences, and is commonly polycistronic, meaning that it encodes more than one protein. In contrast, the mRNA of eukaryotes has a 5ʹ cap, necessary for ribosome binding and for transport out of the nucleus, a poly(A) tail, also necessary for export from the nucleus and for stability, and usually encodes just one protein.

What is Constraining Viral evolution?

Extreme alterations in viral consensus genome do not survive selection The viral genome is one constraint - DNA cannot become RNA, or vice versa - Replication - interaction with host proteins, replication signals - mRNA synthesis signals, poly(A) addition, processing - RNA structure, codon usage Physical nature of capsid - Icosahedral capsids: defined internal space, fixes genome size Selection during host infection A mutant too efficient in bypassing host defenses will kill host, suffer the same fate as one that does not replicate efficiently enough

What are challenges in the development of effective antiviral agents?

Fewer targets against viruses than bacteria, for chemotherapy Viruses replicate intracellularly Some viruses establish latent infections - treating active infection does not cure disease Different viruses e.g. respiratory viruses - cause similar symptoms, making diagnosis difficult Clincial presentation of acute viral illnesses may be at peak viremia - small window which effective treatment possible - specific and rapid diagnostic tests are required Escape from immune surveillance Generation of drug resistance

What are fusion inhibitors?

First class of antiretroviral medications to target HIV replication cycle extracellularly Fusion inhibitors act extracellularly to prevent fusion of HIV to the CD4 molecule

What is the major steps of integration, HIV viral integrase?

First step of integration: removal of 2 nucleotides from each 3' end of the dsDNA within the PC. Leaves free 3'OH groups and 5' overhangs Integrase uses the two recessed 3'OH groups to attack the DNA backbone of the recipient host chromosome - Covalent bonds form between host DNA and retrovirus cDNA Host enzymes remove 5' overhangs and extend the free 3'OH groups to fill gaps - newly synthesized sequences Nicks in the DNA are repaired - covalent bonds synthesized by host ligase (shown in red) Resulting proviral DNA lacks two base pairs, flanked by direct repeats of host DNA - Clue of the presence of provirus sequence

Among pandemic influenza strains how are they caused?

Genetic recombination and antigenic shift among pandemic influenza strains - Antigenic shift Distinct viruses infecting the same cell can reassort, leading to the emergence of strains that can cause human pandemic influenza Antigenic drift may enable avian viruses to gain the ability to infect human cells and be transmitted from person to person

How does HIV exhibit high levels of genetic diversity and transferred from apes to humans on four occasions?

Genetic relatedness of HIV-1 and SIV strains HIV-1 and SIV were isolated from people, one of two subspecies of chimp (troglodytes or schweinfurthii), or gorillas, and their genetic relatedness determined by sequencing complete genomes HIV-1 types M and N are most similar to SIVcpz, indicating that they were zoonotically acquired from the chimpanzee subspecies troglodytes. HIV-1 type O is similar to SIVgor: it was zoonotically acquired from a gorilla SIVgor originated recently by crossing the species barrier from chimpanzees into gorillas

What are Negative(-) strand RNA viruses when it relates to translation?

Genome of negative or minus(-)strand RNA viruses cannot be used directly as mRNA Viruses package RdRp within the virion RdRp synthesizes plus (+)strand ie. mRNA is synthesized from a protein-coated (-)RNA template Most replicate in cytoplasm, a few (eg. Influenza virus) replicate in nucleus Viral genomes are often tightly associated with nucleocapsid (N) protein Two major groups of (-)ssRNA viruses that affect humans: the Mononegaviruses and Orthomyxoviridae Include: - Rhabdoviridae (Rabies virus) - Filoviridae (Ebola virus) - Paramyxoviridae (Measles virus) - Orthomyxoviridae (Influenza virus)

What is used as template for genome replication, -ssRNA virus

Genome replication occurs through a (+) strand intermediate (the antigenomes) called cRNP cRNP differs from mRNA in several ways, though they are both + strands the 5' end of mRNA is composed of host sequences (snatched caps), with a 3' poly-A tail. cRNP is a 'faithful' copy of the vRNP cRNPs are retained in the nucleus, vRNPs are targeted for export cRNP synthesis occurs during early infection and for a short duration relative to the rest of the replication cycle

What is the process of reverse transcription in HIV-1?

Genomic RNA is bound to tRNA, that is hybridized to viral RNA at the primer binding site (PBS) (1) First strand (-) cDNA synthesis is initiated in 5' direction. RNase H activity degrades the small fragment of complimentary templates RNA (2). This allows for the first jump (3) to occur. Complimentary R (R') within the newly synthesized (-) cDNA is complementary to R in the 3' end of the RNA template, allowing for reverse transcriptase extension (-) cDNA extension occurs towards the 5' end of the template (3), with RNase H activity degrading the template RNA (5), leaving behind only the RNA complementary to PPT' (6) PPT' provides a primer for the synthesis of double-stranded cDNA (+), complementary to the (-) cDNA. (7) RNase H activity removes all remaining RNA templates allowing for the second jump - with PBS from the second strand, complimenting the PBS' of the 5' end of the (-) cDNA (8) The result is double-stranded DNA, with long repeats (LTRs) at both ends, containing U3, R and U5

What is Group 7?

Group 7(+/-) dsDNA - RT dsDNA viruses with a gapped genome, with an RNA intermediate Immediately upon infection of cell, DNA gap is repaired by cellular DdDp - a covalently closed circular form of vDNA is synthesized: cccDNA cccDNA is template for transcription of viral mRNA and subgenomic/pregenomic RNA - this serves as template for the viral reverse transcriptase (RdDp) , for production of viral DNA genome

How were viruses culture

Growth of virus in eggs Before the development of cell culture, many viruses were propagated in embryonated chicken eggs Today this method is most commonly used for growth of influenza virus - for vaccine production Egg is placed in front of a light source ("candled") to locate a non-veined are of the allantoic cavity just below the air sac. Virus is injected into the allantoic cavity where it Growth of virus in laboratory animals In early 1900s freezers and cell cultures not available, it was necessary to maintain virus stocks by continuous passage in animals

How does HBV establish infection?

HBV establishes chronic infection by evading innate Immune responses HBV acts like a stealth virus early in infection and remains undetected by innate immune system sensors - spreads until onset of adaptive immune response several weeks after infection Relative invisibility of HBV to innate sensing machinery of cells reflects its replication strategy: - Transcriptional template - cccDNA - is sequestered in cell nucleus - Capped and polyadenylated viral mRNA is produced that resembles normal cellular transcripts - Replicating viral genome is sheltered within viral capsid in the cytoplasm - does not trigger an innate immune response Virus replication is controlled when CD8+ CTL enter liver, recognize antigen, kill infected cells and secrete IFNgamma

What does HBV reverse transcription involve?

HBV reverse transcription involves the viral polymerase (P) - Bound to 5' end of (-) DNA in the viral genome Rt in the Hepadnaviruses is used as part of assembly from the pregenomic RNA (pgRNA- shown below ) pgRNA is both translated and used as genomic DNA template Several features of pgRNA necessary for RT: Three direct repeats (DR): two ((DR1) are identical, found 5' and 3' Two copies of an 'epsilon' sequence (UUCA) - one folds into a stem-loop with a bulge

How are Hepatitis transmitted?

HBV, HCV and HDV are transmitted parenterally, and HAV and HEV are transmitted enterally

What is the Global prevalence and genotype distribution of hepatitis C virus infection in 2015?

HCV genotypes are divided into eight recognized genotypes and 87 subtypes on the basis of sequence variation in the envelope glycoproteins of HCV Globally, genotype 1 (G1) is the most common (46%), followed by G3 (22%), G2 (13%), and G4(13%) - In Australia, G1 and G3 are the most common genotypes - These genotypes are more commonly detected in people who inject drugs

What are some viruses that delay apoptosis in order to complete their replication cycles before the host cell dies?

HHV-8 aka KSHV, the cause of Kaposi's sarcoma, encodes a viral FLIP (v-FLIP) KSHV also encodes a Bcl-2 homologue (vBcl-2) Vaccinia virus CrmA protein inhibits host proteases, including caspases

What is the HIV quasispecies: mutation and bottlenecks?

HIV and other RNA viruses thus exist as dynamic distributions of non-identical but related genomes or quasispecies Bottleneck replication is produced in vivo when a selective pressure (e.g. in the form of antiviral treatment) is applied on the quasispecies, making the drug resistance mutations detectable in the consensus sequence of the virus The 'quasispecies cloud' is the mutant spectrum derived from the dominant master copy The genome of a virus which exists as a quasispecies is really the weighted average of a large number of different individual sequences. It is unlikely that a genome with the consensus sequence is actually replicating. Selective forces in the host determine the surviving virus population

What is HIV and the Nervous System?

HIV enters the nervous system early, at the time of initial infection, and may immediately cause symptoms, or may cause symptoms any time during the person's lifetime HIV easily crosses the blood-brain barrier Primary HIV disease can lead to: - AIDS Dementia Complex (brain) - Peripheral Neuropathy (nerve) - Meningitis (acute or chronic) Sustained viral replication and high viral load is associated with brain tissue inflammation, permanent cell death & HIV-associated neurocognitive disorders

What are Integrase Inhibitors?

HIV integrase is responsible for the transport and attachment of proviral DNA to host-cell chromosomes, - allowing transcription of viral proteins and subsequent assembly of virus particles Proviral integration involves 2 catalytic reactions: - 3'-processing in the host-cell cytoplasm to prepare proviral strands for attachment - Strand transfer whereby proviral DNA is covalently linked to cellular DNA INSTIs competitively inhibit the strand transfer reaction by binding metallic ions in the active site

What is the structure of reverse transcriptase and locations of drug-binding sites in HIV-1 RT?

HIV reverse transcriptase is a heterodimer composed of 2 subunits (p66 and p51). Nucleoside RT inhibitors (NRTIs) bind at the Pol active site, and non-nucleoside RT inhibitors (NNRTIs) bind in a nearby hydrophobic binding pocket.

How does HIV-1 provide a classic example of concerted viral assembly

HIV virion consists of the Env proteins SU and TM, followed by MA matrix protein. Inside of the MA ring, there is a cone-shaped capsid made of the CA protein. The diploid RNA genome closely associated with the NC protein inside the CA. The virion contains the enzymes protease, reverse transcriptase, and integrase, as well as the p6 protein HIV virions also contain a specific tRNA molecule annealed to the RNA genomes Virion also contains the accessory proteins Vif, Vpr, Vpx, and Nef

What are the HIV-1 subtypes?

HIV-1 clades thought to have arisen through recombination Some recombinants may have emerged through natural selection based on their transmission efficiency: eg. SE Asian E/A CRF has spread more rapidly than subtype B in the region Recombination is an important mechanism for evasion of drug or immune pressure

What is the Progression from HIV-1 Transmission to Productive Clinical Infection?

HIV-1 must traverse several tissue layers in the female vagina or rectal mucosa to come into contact with appropriate receptive cells. The CCR5 (R5) viral strain has selective transmission advantages, and R5 variants make up the majority of transmitted and founder viruses. CXCR4 (X4) variants are transmitted only rarely. Founder viruses come into contact with Langerhans' cells or CD4 T cells in squamous epithelium; CD4 T cells can also be infected by viruses bound to submucosal dendritic cells. 1. Initial interaction between gp120 and CD4 2. Conformational changes in gp120 allows for interaction of gp120 V3 loop and coreceptor CCR5

What is the general HIV replication cycle?

HIV-1 reverse transcription occurs in the cytoplasm (1) with dsDNA transported to the nucleus (2). Viral dsDNA integrates into a host chromosome using viral integrase (3). Viral genes are transcribed by host Pol II t produces typical eukaryotic mRNA (4). mRNA is transported to the cytoplasm (5) where translation occurs (6). Some proteins enter the nucleus to affect gene expression (7). (8) genome-length mRNA is synthesized which is then transported to the cytoplasm (9) and packaged (10)

What is the Subunit vaccine, Human papilloma virus(HPV) vaccine?

HPV vaccine is a non-infectious virus like particle(VLP) HPV infection causes warts and cancer - including cervical, penile, vula, anal, and oropharyngeal cancer HPV is a group of >100 types, at least 14 cancer causing Quadrivalent vaccine includes HPV types 6,11, 16, & 18

How does Herpesviridae maintain latency

HSV encodes microRNAs (miRNA) that inhibit viral proteins that control transcription and replication HSV encodes two LATs (Latency associated transcripts) that inhibit apoptosis in neurons To maintain latency: lytic gene expression must be blocked Host cell responses, such as apoptosis and innate immunity, must be blocked Acquired immune response must be evaded or blocked so that infection cell is not cleared

What do HBV and HCV cause?

HVB and HCV can cause chronic infection, causing cirrhosis and hepatocellular carcinoma (HCC)

What is the Clinical and virological course of acute infection with HBV?

Hepatitis B surface antigen (HBsAg) is detectable in blood soon after infection Clearance of HBsAg from blood, and appearance of anti-HBs, indicates recovery Persistence of HBsAg (> 6 months after infection), lack of anti-HBs, indicates chronic infection - carrier state

What are Hepatitis B virus ccc?

Hepatitis B virus ccc (covalently closed circular DNA) cccDNA is also known as episomal DNA or as a minichromosome Following hepatitis B infections, cccDNA can remain following clinical treatment in liver cells and can rarely reactivate The relative quantity of cccDNA present is an indicator for HBV treatment

How does Hepatitis C virus(HCV) block rb?

Hepatitis C virus (HCV) NS5B protein interacts with Rb in the cytoplasm and recruits the E3=ubiquitin ligase E6AP to facilitate ubiquitinoylation of Rb = this targets Rb for degradation in the proteasome Loss of Rb results in dysregulation of many Rb=controlled processes, e.g. compromised cell cycle checkpoints that guard against p53-dependent apoptosis

What are the effects of Hepatitis C?

Hepatitis C virus (HCV) constitutes a significant health burden worldwide. Indeed, this virus has a high propensity for establishing a chronic infection and it is estimated that 130-170 million people suffer from chronic hepatitis C. In the long-term, this can lead to advanced liver fibrosis, cirrhosis and hepatocellular carcinoma. As a consequence, HCV is the most common indication for liver transplantation in developed countries Treatment is now more than 95% effective at curing hepatitis C

What is Hepatocellular carcinoma caused by

Hepatocellular carcinoma can be caused by HBV or HCV infection Both HCV and HBV cause the same type of cancer, hepatocellular carcinoma Oncogenesis is associated with persistent ongoing viral lytic replication and not with latent infection Infection of the liver results in chronic inflammation and oxidative stress, which can progress to a condition called cirrhosis Cirrhosis can on its own be fatal even if it does not progress to cancer.

When/how does Herpes simplex virus establish latent infection

Herpes simplex virus establishes latent infection in trigeminal ganglia Often infected in utero or during birth (80% of babies) Incubation 8-12 days Primary infection usually inapparent, but can result in combinations of fever sore throat, ulcerative and vesicular lesions, gingivostomatitis, edema, swollen lymph nodes, anorexia, malaise

What is Avian influenza A

Highly pathogenic avian influenza HPAI A(H5N1) and H7N9 Transmission largely via direct contacted with infected birds; Human-human transmission is infrequent High fever, cough, shortness of breath and rapidly progressing severe pneumonia. Complications include acute respiratory distress syndrome (ARDS), septic shock and multi-organ failure requiring intensive care At least 1560 laboratory-confirmed human of H7N9 cases since 2013, including at least 615 deaths (mortality rate ~40%)

How does Herpesvirus latency influenced by adaptive immune responses?

Host immune response against the virus has been reported to be involved in the maintenance of a latent state by HSV-1 in neurons HSV-1-infected neurons have been shown to be surrounded by T cells in the TG, presumably limiting viral reactivation which would otherwise lead to lytic replication of the virus, thus hampering the generation of infectious virions from these cells HSV-1 specific CD8+ in contact with TG neurons were shown to block viral reactivation through the release of granzymes that degrade viral proteins In contrast, viral persistence in the ependymal zone of the brain was related to T cells expressing exhaustion markers [eg. programmed death-1 (PD1)] Isolated T cells were unable to control HSV-1 infection ex vivo and secreted less interferon (IFN)-γ in comparison to T cells isolated from TG Reactivation is also triggered by weakening of immunity brought about by aging or by infections such as HIV

What is Passive Immunization for Viral infections

Human immune globulin - Prevention of hepatitis A - Prophylaxis and treatment of enterovirus infections in neonates and in children with antibody deficiency - Treatment of B19 parvovirus infection in immunodeficient individuals CMV immune globulin - Prophylaxis of CMV in solid organ transplant recipient - Treatment of CMV pneumonia in combination with ganciclovir Hepatitis B immune globulin - Prophylaxis of hepatitis B infection Rabies Immune globulin - Post-exposure prophylaxis for rabies (in combination with rabies vaccine) Varicella-zoster immune globulin - Prevention of varicella in immunocompromised and adults within 96hrs of exposure

What are some viruses that subvert apoptosis in order to complete their replication cycles?

Human papillomavirus (HPV) and HIV trigger apoptosis by activating caspase 8 HIV processes procaspase 8, releasing active caspase 8 HPV promotes oligomerization of caspase 8, enhancing its activity Apoptosis may allow the virions to be released after cell death Alternatively, surrounding cells may take up the apoptotic bodies that are full of virions and thereby acquire the viral infection Death by apoptosis avoids inflammation, which is characterized by an influx of immune cells, so HPV and HIV may also use apoptosis to avoid an immune response

Why is it medically important that emerging viruses are typically zoonotic?

Humans enter new landscapes, disturbing them with new housing and economic opportunities Humans contact many animal viruses, some of which will be able to jump the species barrier Most emerging viruses originate in mammals. Viruses that infect mammals such as bats, camels, chimpanzees, and swine are already adapted to many of the conditions that would make it possible for them to replicate in humans

What is the Type I IFN signal transduction cascade?

IFNα/β binds to its receptor, JAK1 and TYK2 are activated and form a complex with STAT1 and STAT2 (1) JAK and TYK2 then phosphorylate STAT1 and STAT2, which subsequently dimerize (2) The phosphorylated heterodimer forms a complex with the IRF9 transcription factor (3). The complex enters the nucleus where it activates ISG transcription (4).

How may glycosylation of viral proteins alter antigenicity

IV HA evolves at the highest rate compared to other influenza viral proteins Presence and acquisition of N-linked glycosylation sites on HA plays a crucial role in immune evasion Number of glycosylation sites on HAs appears to derive from a balance between functionality and immune evasion

What is the process of Influenza virus assembly?

IV proteins are synthesized in the cytoplasm and on the endoplasmic reticulum. Viral proteins that will become part of new vRNPs must be trafficked to the nucleus (black arrows) while the viral envelope proteins traffic to the plasma membrane (red arrows). New vRNPs are synthesized in the nucleus and are then exported to the cytoplasm. They travel along the microtubule network at the periphery of the cell, bundling along the way. Eight different vRNPs gather under a patch of plasma membrane containing matrix and spike proteins. The new virion buds away from the surface of the host cell.

How has the acute viral infection, influenza been of public importance?

IVA undergoes genetic shift and causes pandemics (-) ssRNA virus which undergoes mutation and reassortment: high rates of antigenic variation Antigenic drift The immune response to IV infection drives evolution of the virus to more diverse variants that escape neutralizing antibodies Antigenic shift Evolution to new IV variants that have not been seen in humans before, is mediated by reassortment of zoonotic IVA

What are Post-attachment Inhibitors?

Ibalizumab (humanized monoclonal antibody) binds to domain2(D2) of CD4 and prevents normal structural, conformation change required for attachment Result is to prevent viral entry into target cell

How does mealeas evade immune response?

Immune evasion by cell-to-cell spread in neurons Transport of measles virus RNP complexes from infected neurons to uninfected cell is mediated by microfusion events at the cell membrane where viral F proteins bind neurokinin-1 receptors - facilitates membrane fusion VIral RNP complexes accumulate at cell membrane and pass through In neurons there is incomplete assembly of virus particles at the membrane and budding of virus does not occur - this prevents antibody detection of free virus and promotes latency in brain

What are Importins?

Importins are cellular proteins that transport cargo proteins from the cytoplasm to the nucleus, aided by nuclear localization sequences (NLS)

What was the Discovery of HIV?

In 1983 a retrovirus was isolated from the lymph node of a patient with lymphadenopathy at Institute Pasteur, Paris ʹ Lymphadenopathy associated virus (LAV) In 1984 a cytopathic, T-cell tropic retrovirus was isolated from the blood of patients with AIDS ʹ Human T-cell lymphotropic virus (HTLV-III) In 1984 a similar retrovirus was isolated from blood of patients with AIDS ʹ AIDS associated retrovirus (ARV) EM assessment of virus morphology showed the viruses were morphologically similar to a known group of retroviruses, the lentiviruses In 1986 a morphologically similar but antigenically distinct virus which caused AIDS in patients in west Africa was discovered HIV-2 was distantly related to HIV-1 but was (more) closely related to simian immunodeficiency virus in captive macaques Additional SIV were found in different primates from sub-Saharan Africa These viruses were largely non-pathogenic Identification of SIV in chimpanzees (SIVcpz) and sooty mangabeys (SIVsmm), which were very similar to HIV-1 and HIV-2, respectively, strongly suggested that AIDS had first emerged in both humans and macaques as a consequence of cross-species infections with lentiviruses from different primate species

How can DNA viruses cause productive lyttic infections, cellular transformation, or latent infections

In a lytic infection the host cell dies as a result of producing progeny virions In cellular transformation the host cell begins to be transformed into a cancer cell. The cell becomes less responsive to physiological cues that are meant to regulate cell growth, differentiation, and death. Transformation can be an evolutionary dead end for the virus, if no progeny virions are produced In latent infection the viral genome is mostly quiescent and no virions are produced for a period of time that is much longer than the duration of a lytic cycle (ie. up to the lifetime of the host)

define the term nucleocapsid?

In some viruses, the nucleic acid genome and the capsomeres are so intimately associated that their structure - e.g. SARSCoV-2 nucleocapsid (N protein)

What are the phases of Rabies infection?

Incubation of several weeks to up to 2 years - short in children and for bites to the head or neck Clinical phases: - Prodromal phase - fever, nausea, vomiting, headache, fatigue; some patients experience pain, burning, tingling sensations at site of wound - Furious phase - agitation, disorientations, seizures, twitching, hydrophobia - Dumb phase - paralysed, disoriented and stupor - Progression to coma phase, resulting in death ~ 100% Vaccine (recombinant antigen, human anti-sera or Mab) can be given post-exposure protection, if given before symptoms arise

What was the MERS outbreak, Korea 2015?

Index case was businessman returning from Saudi Arabia - infected 28 others 186 confirmed cases, 38 deaths (20% mortality) 184 nosocomial infections; no community acquired Contributing factors: - Late diagnosis - 'Superspreaders' who were not quarantined - Familial caregiving and visiting - Inadequate hospital infection management - "Doctor shopping" - Main reasons were infection management and policy failures

What is the time course of acute measles infection?

Infection induces 'immune amnesia' that lasts for 2-3 years Measles virus (MeV) infection suppresses the proliferation of lymphocytes Lymphocytes isolated from patients or animals infected with MeV proliferate poorly upon ex vivo stimulation by mitogens

What is the mode of Varicella-Zoster Virus Infection and Spread?

Infection is initiated on conjunctiva or mucosa of URT and spreads to regional lymph nodes Infected T cells enter bloodstream, cause a primary viremia Also invade liver, spleen and other organs, initiate secondary viremia Infected skin-homing T cells invade skin and initiate third round of infection ~ 2 weeks after initial infection - characteristic chicken pox rash appears Virions in skin infect sensory nerve terminals and spread to dorsal root ganglia of the peripheral nervous system, where a latent infection is established Decline in immunity with aging and other factors induces reactivation, and shingles

What is the pathogenesis of Infleunza?

Infection of upper respiratory tract Virus replicates in epithelial cells in nose and sinus passages, killing them Production of IFN and other cytokines accounts for severe malaise Virus infection of lower respiratory tract can occur - influenzal pneumonia: overwhelming toxemia with high mortality. Virus is replicating in alveolar epithelial cells IV infection also enhances chances of stroke and heart disease Avian IV demonstrates strong preference for a(2,3) sialic acid

How does genetic diversity among influenza A viruses arises through mutation and recombination?

Influenza A viruses have (−) ssRNA genomes consisting of 8 different segments; each segment encodes between 1 and 4 of the 17 influenza A proteins Because of the misincorporation rate for its viral RdRp, influenza A virus replication results in about 1 mutation per offspring genome. Every infected cell gives rise to 10,000 mutants

Using Influenza as a model, can you describe the attachment by enveloped viruses?

Influenza virus has two spike proteins: Haemagglutinin (HA) Neuraminidase (NA) (A) Influenza virus, showing the hemagglutinin and neuraminidase spikes on the surface. (B) Hemagglutinin monomer is shown here - the HA exists as a trimeric molecule on the virus surface HA has a receptor binding pocket and a fusion peptide, and crosses the viral envelope. HA spike protein binds to sialic acid - also known as neuraminic acid

What is the assembly of the influenza virus, concerted genome-nucleocapsid assembly, and sequential acquisition of envelope?

Influenza viruses have an envelope consisting of a lipid bilayer including four viral proteins: the HA spike, NA spike, and the two matrix proteins M1 and M2. Internal to the lipid bilayer are eight different vRNPs, each consisting of a single different (−) sense RNA bound to the proteins NP, [PA, PB1, and PB2]. The NP protein coats the whole length of the RNA, whereas the other three proteins [PA, PB1, and PB2] form a trimeric complex found only once per vRNP

What is reassortment, and what viruses undergo this type of recombination?

Influenza viruses have segmented genomes, and recombinant offspring of two different influenza A viruses have genomes composed of a new combination of genome segments, some from one of the parental viruses and one or more from the other This process is termed reassortment

What is the Influenza virus model for replication of an animal virus?

Infulenza (IVA) has 8 genome segemetns with single-stranded negative-sense RNA closely associated with nucleocapsid proteins and enzymes (PB1, PA, and PB2) in a structure known as viral ribonucleoprotein, or vRNP. The vRNPs travel to the nucleus using the cell's cytoskeleton and motor proteins. The viral genome segments must enter the nucleus through nuclear pore complexes before viral gene expression can occur. Viral gene expression and genome replication result in the formation of new vRNPs in the nucleus. The vRNPs are exported through the nuclear pores to the cytoplasm so that they can associate with other virus proteins and acquire an envelope, exit the cell through a process called budding. host dies: the cell's ATP, amino acids, and nucleotides are depleted, leaving the cell unable to maintain homeostasis.

How does Human immunodeficiency virus cause persistent (chronic) infections?

Initial acute infection is followed by years of persistent infection before CD4+ T cell counts decline to levels incompatible with protective immunity Despite initial robust immune response viral replication is ongoing New HIV genomes accumulate mutations very rapidly: HIV has an extremely high error rate that results in 1-2 substitutions in each new virion relative to its ancestor this high level of reproduction in combination with the high error rate mean that HIV evolves during the persistent lytic phase of infection Host immune system puts tremendous selective pressure on the virus, ultimately selecting variants that escape the immune response (=escape variants) Latent virus that exists as a provirus is not actively being expressed and cannot be eliminated with drugs that target viral replication

What is the Viral dissemination of CoV into body organs

Initial replication takes place in the upper respiratory tract, followed by the migration of the virus to the lungs. A primary viremia occurs after establishment of infection and replication in the lung pneumocytes. This viremia disseminates the virus throughout the body via blood stream where another cycle of viral replication takes places and ensuring viremia leads to further dissemination ACE2, Angiotensin-converting enzyme 2; RdRP, RNA-dependent RNA polymerase. ER, Endoplasmic reticulum; ERGIC, ER-Golgi Intermediate Compartment.

What is Polyomavirus JC?

JC virus infection can result in a fatal demyelinating disease of the central nervous system: progressive multifocal leukoencephalopathy (PML) in which oligodendrocytes are destroyed

What is the process of viral entry through receptor mediated endocytosis - clatharin pathway

Key feature of endosomes is progressive acidification due to action of vacuolar ATPase - transports protons. Viruses may enter cells by both clathrin-dependent and clathrin-independent pathways. Virus binding to a receptor triggers internalization through clathrin-coated pits. After internalization, the early endosome acidifies, triggering viral uncoating. Acidification triggers the next stage of uncoating, which is typically to release the nucleocapsid into the cytoplasm. Viruses that enter via clathrin-dependent, receptor-mediated endocytosis e.g. influenza A virus and human rhinovirus.

How do SV40 large T and small t antigens affect the cell cycle and apoptosis

Large T antigen interacts with pRB, preventing pRB from interacting with E2F transcription factors and de-repressing S phase genes. The large T antigen also interacts with p53, which prevents p53 from stimulating apoptosis. The small t antigen interacts with the PP2A (phosphatase) complex and inhibits its activity, thereby preventing repression of S phase genes

What are the types of viral transmission

Latrogenic: activity of health care worker leads to infection of patient Nosocomial: individual is infected while in a hospital or health care facility Vertical: transfer of infections between parents and offspring Horizontal: all other forms of transmission Germ line: transmission as part of host genome (eg. Integrated proviral DNA)

What is a method of deriving live attenuated vaccines

Live-attenuated viral vaccines have modified genomes and less virulent then wild-type Antigen are similar enough to WT to induce immune response that protects against WT infection/disease May be more potent than killed/inactivated/ nonreplicative antigens as they infect target cells and induce broad range of effector immune responses, including CD8+ T cells

What are the Cells and molecules of the adaptive immune response?

Lymphocytes are the cells of the adaptive immune response and include CD4+ TH cells, CD8+ CTL cells, and B cells B cells synthesize antibodies, which are responsible for humoral immunity T cells mediate cellular immunity and 'help' B cells to produce antibodies

What is Middle East Respiratory Syndrome (MERS)?

MERS Coronavirus (MERS CoV) Enveloped; ssRNA(+) genome 27-32kb Causes severe acute respiratory illness with fever, cough, shortness of breath; pneumonia; respiratory failure At the end of July 2019, a total of 2458 laboratory-confirmed cases of MERS, including 848 associated deaths (caseʹfatality rate: 34.49%) Reported in 27 Countries - cases linked to residence in, or travel to, Arabian Peninsula

What is the HIV replication cycle and targets for antiretroviral drugs?

Main classes of antiretroviral compounds: - Fusion inhibitors; - Entry inhibitors; Chemokine receptor antagonists; - Reverse transcriptase inhibitors (nucleoside and non-nucleoside) - Integrase inhibitors; - Protease inhibitors

What is the MHC Class I?

Major Histocompatibility Class I molecules are responsible for 'sampling' the cell cytoplasm contents and presenting that for inspection by other cells of the immune system. In a healthy, uninfected cell, the peptides or epitopes 'presented' are normal self-antigens. In an infected cell, MHC Class I molecules present viral epitopes to the cells of the immune system, triggering antiviral responses.

What are LRT(Lower respiratory tract) infections?

Major acute viral infections of the lower respiratory tract are caused by: Influenza virus and Respiratory syncytial virus Common characteristics of infection are short incubation (1 to 4 days) and transmission from person-to-person Transmission can be direct, through droplets, or indirect, through hand transfer of contaminated secretions

What is a malignant tumour?

Malignant: uncontrolled growth that can invade nearby tissues and also spread to other parts of the body through blood and lymph - Carcinoma: a malignancy that begins in skin or in tissues that line or cover internal organs - Sarcoma: begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue - Leukemia: starts in blood-forming tissue, such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter blood - Lymphoma and multiple myeloma begin in cells of the immune system - Central nervous system cancers begin in brain and spinal cord

What are Viral rashes and poxes?

Many infections, including those caused by measles virus, smallpox virus, and varicella-zoster virus, produce a characteristic rash or lesion over extensive areas of the body, even though the primary infection began at a distant mucosal surface. This phenomenon results when the primary infection escapes the local defenses and virus particles or infected cells spread in the circulatory system to initiate foci of infected cells in the skin. Th1 cells and macrophages activated by the initial infection home to these secondary sites and respond by aggressive synthesis of cytokines, including IL-2 and IFN-γ. Such cytokines then act locally to increase capillary permeability, which is partially responsible for a characteristic local immune response referred to as delayed-type hypersensitivity. This response, which usually requires 2 to 3 days to develop, is the basis of many virus-promoted rashes and lesions with fluid-filled vesicles

What are Medical treatments for HIV-dementia complex?

Many types of HAART do not easily cross into the brain in laboratory studies However, HIV-infected individuals may show increased permeability of the BBB HAART usually reduces viral load both in the periphery and in the CNS Reduction of viral load in the CNS is associated with reduced cognitive symptoms (improvement of cognitive functions) Patients with stable viral load do not show increased risk for cognitive decline, even after 5 years of monitoring

What is the Viral Evasion of complement?

Many viral genomes encode proteins that can interfere with complement. E.g - Dengue NS1 targets C4 - Smallpox SPICE (smallpox inhibitor of complement enzymes) - Influenza M1 interacts with C1qA (part of the C1 complex)

What is the Viral evasion of MHC class I presentation?

Many viruses encode one or more proteins which target different steps of the MHC class I antigen presentation process. Producing abundant viral protein that is resistant to degradation by the proteasome reduces viral epitope display e.g. Epstein-Barr virus (1). Several herpesviruses encode proteins that block the function of TAP, preventing transport of peptides from the proteasome into the ER (2). Another evasion strategy is to target vesicles containing MHC-I-epitope complexes to the lysosome so that the complexes get degraded and never reach the plasma membrane (3). Viruses can also encode proteins that block MHC-I- epitope complexes from leaving the Golgi apparatus so that they never reach the plasma membrane (4).

What is Neural Spread

Many viruses spread from primary site of infection by entering local nerve endings Viruses that infect the nervous system are neurotropic Virus replication usually occurs first in non-neuronal cells, with virions spreading into effect (e.g. sensory) or efferent (e.g. motor) fibres innervating the infected tissue Cells of peripheral nervous system are usually infected first; virus then spreads to spinal cord and brain (CNS) Herpes simplex virus becomes latent in peripheral neurons that innervate site of infection Reactivation from latency results in viral replication in primary neuron and transport of progeny virions back to peripheral tissue (to form a cold sore), or to the CNS (to cause lethal viral encephaltitis)

What is the Morphological rearrangement of retrovirus particles upon proteolytic processing of the Gag polyprotein.

Maturation is defined as any irreversible process that occurs during or after viral release that takes the assembled virus from a noninfectious state to an infectious one These two cryo-electron micrographs show the maturation of human immunodeficiency virus type 1 virus particles Left: the immature particles contain a Gag polyprotein layer below the viral membrane and its external spikes Right: processing of Gag converts such particles to mature virus particles with elongated cone-shaped internal capsids

What is the Maturation of influenza virus HA protein during transit along the secretory pathway

Modifications that occur during transit of the influenza virus HA protein through the various compartments of the secretory pathway: In the ER, these are translocation and signal peptide cleavage (1), disulfide bond formation, and addition of N-linked core oligosaccharides (2), as the protein folds (3). Oligomerization also takes place in the ER lumen (monomeric form of HA showed here) N = asparagube O = serine or threonine Production of viral envelope glycoproteins involves addition of N- (and O-) linked oligosaccharides as the proteins travel the secretory pathway. Such modification is the result of sequential action of several host cell glycosidases & glycolsyltransferases located in the ER & Golgi compartments

How do some +ssRNA viruses translate structural proteins through subgenomic RNA

More complex replication for some +ssRNA viruses - have 2 distinct stages of gene expression that involves translation of proteins through subgenomic RNA Alphaviruses such as Chikungunya, Ross River virus, Sindbis virus (SINV - model alphavirus) Coronaviruses, including SARS-CoV-2 Genome divided into separate regions - encode non-structural and structural polyproteins, separated by a non-coding junction Early stage gene expression: expression of non-structural proteins Later stage gene expression: expression of structural proteins

What do dsDNA animal viruses rely on from host?

Most Baltimore Class I (dsDNA) animal viruses rely on host transcription machinery for gene expression Most DNA viruses of eukaryotes transcribe and replicate their genomes and assemble progeny in the nucleus, the site of cellular DNA transcription and replication (exceptions include the poxviruses, which replicate their DNA genomes in the cytoplasm) Most human cells do not divide or do so rarely Viruses do not replicate well in quiescent cells Viruses must induce host cell replication proteins (directly associated with virus size) Virus-encoded early gene products regulate this, and put cells into synthesis (S) phase Proteins required for synthesis: - DNA polymerase & accessory proteins - Origin binding protein, helicases - Exonucleases - Enzymes of nucleic acid metabolism (eg. Thymidine kinase)

How do most viruses synthesise RNA?

Most Viral genomes are RNA RNA-dependent RNA polymerase (RdRp) is an essential protein encoded in the genomes of all RNA-containing viruses with no DNA stage Cells do not have RdRp to replicate virtual RNA genomes or to synthesise mRNA from viral RNA template RNA viruses encode viral RdRp (RdRp can be packaged into the virus e.g. (-) RNA viruses) Viral RdRp synthesises mRNA which is readable by cellular ribosomes

What are Arboviral diseases of public health importance?

Most arboviruses causing human disease belong to three families; Togaviridae (genus Alphavirus), Flaviviridae (genus Flavivirus) and Bunyaviridae (Bunyavirus, Orthobunyavirus, Nairovirus and Phlebovirus genera) The alphaviruses and flaviviruses are enveloped, linear single-stranded, positive sense RNA viruses. They are spherical in shape, with an underlying capsid and measure from 40 to 70 nm. The bunyaviruses are enveloped, segmented, circular negative-strand RNA viruses. They are generally spherical and measure 80-120 nm in diameter vast majority of arboviral infections lead to either an asymptomatic or non-specific mild illness e.g. arboviral diseases Dengue virus (DENV), West Nile virus (WNV), Zika virus (ZIKV) and yellow fever virus (YFV), Chikungunya and rift valley fever virus (RVFV)

How does virus entry occur via respiratory tract?

Most common route of viral infection Large absorptive area of human lung (140 m2) and high resting ventilation rate (6 L air/minute),large number of foreign particles and aerosolized droplets are introduced into the lungs with every breath Numerous host defense mechanisms: - Mechanical barriers eg. Mucocilliary blanket of ciliated cells, mucous-secreting goblet cells, and subepithelial mucous-secreting glands trap foreign particles and swallow them or move them from lungs to throat - Macrophages lining alveoli ingest and destroy particles enter respiratory tract in the form of aerosolized droplets expelled by an infected individual by coughing or sneezing Virus can be transmitted through contact with saliva from an infected individual

What is the infection of the West Nile virus?

Most infections are asymptomatic 20% if infected individuals may develop symptoms, including headache, body aches, joint pains, vomiting, diarrhea, or rash Less than 1% develop severe illness - meningitis or encephalitis (10% mortality rate) No vaccine or specific antiviral treatments for West Nile virus infection are available

What is the Ross River fever?

Most infections are asymptomatic (~70) Infection causes an acute febrile illness for 2-5 days, followed by a prolonged arthralgic disease that may last for many months - "epidemic polyarthritis"

What is the dsDNA bi-directional replication?

Most nuclear dsDNA viruses replicate via this mechanism, in eukaryotic host cell nucleus Same mechanism used by all cellular organisms DNA replication begins at specific location in genome, the ori Topoisomerase unwinds dsDNA at ori ssDNA-binding proteins cover the ssDNA created in the replication bundle RNA primase synthesizes short RNA primers that are then used by the DNA polymerase to prime DNA synthesis

What is the Flaviviruses, Geographical Distribution?

Most of the world's population is at risk of flaviviral infections. Major human pathogens, including yellow fever, dengue, WNV, St Louis encephalitis (SLEV), Japanese encephalitis (JEV), Murray Valley encephalitis (MVEV), and tick-borne encephalitis (TBEV). Murray valley encephalitis virus and Kunjin virus (a variant of WNV) are endemic to Australia.

What is the viral CNS infection, aseptic meningitis?

Most represent uncommon complications of common systemic infections - meningitis, encephalitis, myelitis and paralysis Aseptic meningitis (not caused by pyogenic bacteria) - Inflammation of meninges - increased mononuclear cell count (mononuclear pleocytosis); normal CSF contain 0-5 MNC per µl - Viral infection is the most common cause of aseptic meningitis - enterovirus are the most common cause - There are non-infectious causes of aseptic meningitis, however, the term is almost synonymous with viral meningitis - Clinical features most commonly include a triad of fever, meningism and vomiting.

How can translation termination be suppressed be a result of multiple proteins being encoded using overlapping RNA sequences?

Multiple proteins can be encoded using overlapping mRNA sequences: Suppression of translation termination Used to produce the less abundant polyprotein P1234 from sequences that overlap with those encoding more abundant P123. RdRp (nsP4) is needed in smaller amounts than other NSPs

How does Viral genetic diversity arises through mutation?

Mutation occurs when a mistake during replication or a physical or chemical assault changes a nucleotide to something different from that in the ancestral genome Cellular DNA polymerases have editing functions that keep the intrinsic rate of nucleotide substitutions very low, but many viral polymerases have no editing functions Editing refers to the process of excising a misincorporated nucleotide and replacing it with the correct nucleotide during replication. Because the viral polymerases lack editing functions, viruses that rely on viral polymerases accumulate mutations at a much higher rate per generation than cells do Viral RdRps are particularly mutagenic; they misincorporate the wrong base approximately 1 in 104 times, with a range of 1 in 10^4 - 1 in 10^5 depending on the RdRp. These values are between 10 and 10,000 times higher than the misincorporation rate of cellular DNA replication Misincorporation is responsible for much more genetic change than physical and chemical assaults, but UV light and radiation are also important sources of mutation

What do RNA viruses use to replicate genomes?

NA viruses replicate their genomes using virally encoded RNA-dependent RNA polymerase (RdRp) RNA genome is template for synthesis of additional RNA strands During replication, at least three types of RNA must be synthesised: - Genome - Copy of the genome (anti-genome) - mRNA - Some viruses also synthesise subgenomic mRNAs RdRp supports all these processes (in association with other viral and cellular proteins: the replicase complex) Some viral RdRps have methylase activities that synthesise mRNA caps Some viral RdRps may 'stutter' at poly A tracts to generate polyadenylated mRNAs

What is the role of NK cell in viral control

NK cell cytotoxic functions are inhibited by self-antigens presented to them by abundant MHC class I on the surface of cells. When these MHC class I molecules are reduced, the inhibitory NK cell receptor is not engaged, triggering NK cells to release effector proteins. Perforin creates channels in the cell membrane, which permits the entry of granzyme proteins ultimately triggering apoptosis of the infected cell.

How do NNRTIs exert their action?

NNRTIs exert their action by attaching to a region of the binding pocket of reverse transcriptase Resistance to NNRTIs can result from mutations that impact amino acids surrounding the binding site thereby preventing the NNRTI from entering into the NNRTI binding pocket

How do naked viruses release virions?

Naked viruses can enter cells by endocytosis and phagocytosis. The capsid has to disassemble in order to release the genome, or the genome has to be extruded from the capsid. Rhinovirus, contracted by inhalation and thus not exposed to low pH until after endocytosis, releases its genome after acidification of an endocytic vesicle. A. The capsid of a picornavirus has VP1, VP2, and VP3 on its surface with VP4 buried in a layer beneath them, not accessible to the surrounding solvent. B. Penetration is enabled by dramatic protein rearrangements, such that some parts of VP4 become displayed on the surface of the virion particle and subsequently form a pore through the membrane. The (+) ssRNA genome is released into the cytoplasm.

What do NK cells target?

Natural killer (NK) cells target cells with reduced MHC-1 display (A) A normal cell has high levels of MHC-I-peptide complexes on its surface, so that the NK cell does not attack the normal cell. (B) An NK cell can detect an abnormal cell with reduced levels of MHC-I-peptide displayed and will subsequently kill the abnormal cell.

What is the mechanism of action of Zanamivir and Oseltamivir?

Neuraminidase inhibitors - Viral neuraminidase catalyzes cleavage of terminal sialic acid residues attached to glycoproteins and glycolipids, a process necessary for release of virus from host cell surfaces Oseltamivor is an analog of sialic acid Cleaves terminal sialic acid residue and destroys receptor Newly formed virions adhere to cell surface; spread of virions is limited

What are HIV-associated neurocognitive disorders?

Neuropathogenic mechanisms that contribute to HIV-associated neurocognitive disorders HIV-infected macrophages and microglial cells release neurotoxic viral proteins that trigger astrocyte activation, which results in increased glutamate release and reduced glutamate uptake. Elevated extracellular glutamate levels cause neuronal bioenergetic disturbances that lead to aberrant synapto-dendritic pruning and neuronal injury. Moreover, systemic inflammation and microbial translocation products lead to microglial activation and increased production of chemokines and cytokines that contribute to neuronal injury.

What Studies that will inform vaccine design and development?

Neutralising antibody response in recovered patients should be characterized: - average titres after asymptomatic, mild, and severe disease - Magnitude and kinetics - Longevity of response Cross-reactive antibodies against HuCoV as context for vaccine studies Studies in animal models to define protective neutralizing antibody titre - human sera from recovered patients with range of Nab titres, to identify a target titre of vaccines

What is the role of Neutrophiles in viral control

Neutrophils produce neutrophil extracellular traps (NETs) in the presence of viral infection. These help control viruses by: - Trapping virions, immobilising them - Contain antiviral components than can inactivate viruses - Stimulate other immune cells

What are Enteroviruses?

Non-enveloped, (+) ssRNA genome Picornaviridae - at least 72 serotypes 5 main groups: - Poliovirus: paralytic poliomyelitis, aseptic meningitis, febrile illness - Coxsackie group A: aseptic meningitis - Coxsackie group B: aseptic meningitis and encephalitis - Echovirus: aseptic meningitis - Enterovirus: meningitis Transmission occur via hand-to-mouth contact Similar to poliovirus in epidemiological and infection

What is the Poliovirus and Poliomyelitis?

Non-enveloped, (+) ssRNA linear genome 3 serotypes (1-3), each with slightly different capsid protein; types 2 and 3 are eradicated Transmitted by faecal-oral route, or via contaminated food or water Multiplies in intestine, enters circulatory system, then CNS Poliomyelitis (polio) ʹ acute enteroviral infection of the spinal cord that can cause neuromuscular paralysis 1 in 200 infections leads to irreversible paralysis; 5-10% of paralysed persons die when breathing muscles become immobilised The paralytic disease occurs mostly in adolescents

What is the Adenovirus?

Non-enveloped, linear, dsDNA genome Adenoviridae >50 serotypes Relatively mild URT infections, but can cause severe bronchopneumonia in infants; croup, gastroenteritis, cystitis and keratoconjunctivitis

What is the history Non-nucleoside Reverse Transcriptase Inhibitors?

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) introduced 1996. NNRTIs exhibit potent activity against HIV-1 NNRTIs bind the p66 subunit at a hydrophobic pocket distant from the active site of the enzyme non-competitive binding induces a conformational change in the enzyme that alters the active site and limits its activity First generation NNRTIs include nevirapine and efavirenz; second generation drugs include etravirine Etravirine can bind site despite presence of some mutations, that limit first-generation agents

What is responsible for viral attachment to host cells?

Noncovalent intermolecular forces (A) A virus spike protein binds to its cellular receptor (B) Close-up on regions of spike and receptor that interact, showing typical non covalent intermolecular forces that hold the spike and receptor together such as ionic bonds, hydrogen bonds, and London dispersion forces (sometimes known as van der Waals interactions)

What is the Endomembrane trafficking of vesicles containing spike proteins?

Normal cellular vesicles move proteins from the rough ER through the Golgi apparatus, where they acquire glycosylation, as do viral proteins passing through the Golgi apparatus. From the Golgi apparatus, glycosylated proteins in vesicles move to the plasma membrane, where the vesicles fuse with the plasma membrane so that the proteins in the vesicles become part of the membrane. The portions of the proteins that had been inside the lumen of the vesicle, where glycosylation enzymes modify the proteins, become the outside (distal) surface of the membrane and, in the case of viruses, will form the exterior surface of the viral envelope.

What is the CoV replication and proofreading complex?

Nsp12-RdRp replicates and transcribes the genome and sg mRNAs Nsp7/nsp8 proteins confer processivity to the polymerase Nsp13 unwinds dsRNA ahead of the polymerase Nsp14-ExoN complexed with its co-factor nsp10 proofreads the nascent RNA strand and excises misincorporated nucleotides Nsp13, an unknown GTPase, Nsp14-N7-methyltransferase, and the Nsp16-2ʹ-O-methyltransferase/Nsp10 complex are involved in the capping mechanism

How does initial infection occur?

Number of virus particles required to initiate and maintain an infection depends on - Particular virus - Site of infection - Age and physiology of host A single virus particle can initiate an infection; complexity of the infectious cycle, and probability of a single virus particle completing the cycle is not 100% Defective virus particles may be produced Virus Infectivity may be determined by assessment of Tissue Culture Infectious Dose (TCID) and by Plaque assay

What are the two groups of retroviruses?

Oncogene-transducing Infection with an oncogene-transducing retrovirus rapidly leads to cancer in nearly 100% of susceptible animals and leads to transformation of cultured cells in nearly 100% of cases. oncogene-deficient retroviruses Infection with an oncogene-deficient retrovirus instead leads to cancer only some of the time, and does so slowly in infected animals; these viruses transform cultured cells in only a minority of cases

Why do Oncogene-transducing retroviruses carry a functional oncogene in genome?

Oncogene-transducing retroviruses carry a functional oncogene in their genomes so that 100% of host cells carrying proviral DNA express the oncogene whenever the proviral promoter in the long terminal repeats (LTR) is active

What does oncogenic mean?

Oncogene: Gain of function An altered gene whose product can act in a dominant fashion to help make a cell cancerous. Usually, an oncogene is a mutant form of a normal gene a "proto-oncogene" involved in the control of cell growth or division.

How can Some viruses can evade the immune response with the role of IL-10?

One of the functions of IL-10 is to suppress immune cell activity at the end of an infection so that formerly infected tissues can go back to normal. Herpesviruses interfere with activation of CTLs through manipulating the cytokine IL-10. Some herpesviruses stimulate host cells to secrete IL-10, and others encode viral proteins that mimic IL-10. The effect in either case is to suppress the activation of CTLs.

What are Anti-Herpesvirus Agents for HSV and VZV?

Oral Agents - Acyclovir, Valacyclovir, Famciclovir Ophthalmic - Trifluridine Topical Agents - Acyclovir, Docosanol, Penciclovir

What is Respiratory Syncytial Virus?

Orthopneumovirus genus, Pneumoviridae family RSV is a ubiquitous pathogen that infects nearly all children by 2 years of age; half have 2 infections by that age Globally, ~60,000 deaths in children <5 yo Symptoms are the same as those for HMPV (Metapneumovirus genus) After infection and replication in nasopharynx virus may spread to LRT - host immune responses increase mucous production and inflammation leading to narrowing of airways and bronchiolitis in children, acute respiratory illness in adults

What are Influenza Agents?

Oseltamivir, Zanamivir, Amantadine, Rimantadine Amantadine/Rimantadine target IVA M2 protein ion channel; block uncoating of IV RNP

What is Vaccinia growth factor activity

Other vaccinia proteins include those that manipulate the host immune response to the virus advantage, or that prevent or subvert the apoptotic response to stress (that would be induced by viral infection) Eg. vaccinia growth factor (VGF) mimics cellular epidermal growth factor - binds to cellular epidermal growth factor receptors and triggers cells to enter the cell cycle and proliferate

What are the outcomes of a virus host interaction dependent on?

Outcomes of a virus-host interaction depend on many factors, including ecological, host, and viral parameters The predominant parameters for spread of infection are the population density and the age and health of individuals in that population. Multiple parameters converge to promote emerging viral infections

How is Human immunodeficiency virus (HIV) is an example of a chronic viral infection?

Over the course of a typical HIV infection, virions are found in very low levels in blood HIV is not a latent infection in which viral replication is not ongoing but instead persists as a chronic infection during which viral replication is ongoing - even when not detectable by molecular tests Within weeks of infection, the number of host cells (CD4+ lymphocytes) in the blood declines It may take years for the host CD4+ T cells to become depleted and drop <200 mL−1, diagnostic of acquired immunodeficiency syndrome (AIDS) patient becomes susceptible to many infections and eventually succumbs.

How do most dsDNA viruses prevent or delay cellular apoptosis?

P53 is a key protein regulator of apoptosis in response to DNA damage - Both DNA damage & viral infections activate p53 When p53 is activated, it becomes phosphorylated, which has two major effects: (1) stimulates cells to undergo apoptosis (2) prevents the pRB protein from becoming phosphorylated - if phosphorylated it would detach from E2F and transcription would proceed DNA viruses therefore usually block p53 in order to prevent apoptosis and to enable phosphorylation of pRB Preventing apoptosis provides the virus with sufficient time to complete its replication cycle while enabling phosphorylation of pRB forces the host cell past the G1 checkpoint

How do TLR-3 and RIG-1 recognise dsRNA?

PAMP (dsRNA) is recognised by PRR: transmembrane protein TLR- 3 or RIG-1 (in the cytoplasm), then PRR undergoes conformation change - signal transduction cascade, then Innate immune response (cytokine secretion)

What are packaging signals?

Packaging signals are repeats of short sequences, some of which are also part of viral promoters or enhancers; they are positioned close to an origin of replication

What is the papillomavirus gene expression & DNA replication within stratified epithelium?

Papillomaviruses use early proteins to manipulate the host cell cycle and apoptosis The cells in the two lowest layers of the stratified epithelium are actively reproducing, thus providing DNA replication proteins to the virus The remainder of the epithelium consists of differentiated cells that are not regularly dividing as they are pushed toward the distal parts of the stratified epithelium In order to accomplish vegetative genome replication, the virus must force the quiescent host cells in the midzone to express host DNA replication proteins. Two virus proteins, E6 and E7, are crucial for this process and interact with pathways controlled by p53 and pRB Normally, p53 promotes apoptosis in stressed cells such as those infected by a dsDNA virus The E6 protein of papillomaviruses targets the p53 protein for proteolytic degradation, thereby preventing p53-triggered apoptosis. The E7 protein binds to pRB; pRB cannot bind to E2F transcription factors Consequently, the E2F transcription factors no longer repress the expression of DNA replication S phase proteins.

Wha is the Transmission of Hepatituis B

Parenteral transmission - Organ transplantation, blood transfusion, needlestick injury, needle sharing, tattooing Sexual Intra-familial (sharing personal items such as razors) Australia: Injecting drug users, MSM, inmates, immigrants from endemic regions, Aboriginal and Torres Strait Islander peoples

What is the Hepatitis B virus

Partially double-stranded circular DNA of about 3.2kb 4 overlapping open reading frames (ORFs: S, C, P, and X) that encode the viral HBV surface proteins (HBsAg), structural core protein (HBcAg), polymerase, and nonstructural precore proteins (secreted e-antigen (HBeAg), and the X protein)

How can viruses within second stage penetrate into host?

Penetration and uncoating and, if necessary, transport to the nucleus Penetration is the entry of the virion or subcomponents of the virion into the host cell. (A) Release of viral genome into the cytoplasm through a pore. Eg. poliovirus forms a pore in the host cell membrane and releases its (+) RNA strand genome directly into the host cytoplasm, after which its genome can be translated. (B) Fusion of enveloped virus at the plasma membrane, releasing the nucleocapsid into the cytoplasm and leaving viral spike proteins on the cell surface. Eg. the enveloped togaviruses - penetration occurs when the virus is internalized into an endocytic vesicle that fuses its envelope with the endocytic membrane and releases its nucleocapsid into the cytoplasm. Uncoating then occurs when the nucleocapsid disassembles and the (+) ssRNA genome can then be translated. (C) Endocytosis of a virus followed by release of the nucleocapsid into the cytoplasm; no viral proteins are left on the cell surface. For many viruses penetration includes internalization of the entire virion - selective advantage as no viral proteins on the surface of the host cell where they might alert the immune system.

What is NK-mediated apoptosis?

Perforin secreted by an NK cell oligomerizes and forms a pore Granzymes secreted by the NK cell enter the cell through the perforin channels The granzymes trigger apoptosis.

What is the Passive Immunity of transplacental transfer of maternal IgG to developing foetus?

Period when infants are particularly prone to infection: maternal antibodies at low levels, infant's own IgG still at low levels

What are persistent infections & types?

Persistent infections are those in which the virus, its genome, or parts of its genome persists in its host for the long term - months, years, or the duration of an infected person's lifetime Two main types of persistent infection: Chronic infections - lytic replication in a multicellular organism occurring at low levels and ongoing for longer the duration of the cell division cycle of most host cells - the immune system takes a long time to eliminate the virus from the body Latent infection - virus exits the lytic cycle and persists in host cells, usually in the form of a few nucleic acids and proteins, without causing production of new virions. Viral genomes persist even when viral proteins are not detectable. Exit from latency and entry back into the lyric cycle typically occurs when the host cell encounters environmental stress.

What is the infection of the Poliovirus and Poliomyelitis?

Poliovirus infect mucosal cells in oropharynx and intestine, multiply in number and shed in throat and faeces, some leak into blood Most infections are short-term with mild viraemia - non-specific symptoms including fever, headache, nausea, sore throat and myalgia If viraemia persists, virus spreads to spinal cord and brain - nervous tissue is infected but not destroyed - Muscle pain and spasms, meningeal inflammation and vague hypersensitivity - Invasion of motor neurons causes flaccid paralysis progressive muscle deterioration; occurs in 25-50% of patients infected with polioviruses in childhood

What are Polyomaviruses, e.g. Simian virus 40(SV40)?

Polyomaviruses are small DNA viruses that drive cells into S phase Polyomaviruses are associated with post-organ transplant kidney malfunction and with Merkel cell carcinoma Prototype virus is simian vacuolating virus 40 (SV40) Smallest dsDNA viruses that infect animal cells - non-enveloped spherical virions with 4- to 5-kbp circular dsDNA genome

What are the correlates of protective immunity against HIV-1?

Possible requirements for protective immunity against HIV-1 infection: - Cytotoxic lymphocyte activity (CD4+ and CD8+ T cells) - Innate immune responses (plasmacytoid dendritic cells) - NK cell activity - Antibody-dependent cellular cytotoxicity - Neutralising antibodies

What are Poxviruses

Poxviruses are extremely large dsDNA viruses that replicate in the host cytoplasm The poxviruses are the largest dsDNA viruses that infect humans Variola virus causes smallpox; vaccinia virus is antigenically very similar and is the immunogen for the smallpox vaccine The linear genome inside is composed of 194 kbp of dsDNA with inverted terminal repeats that form covalently closed hairpin termini dsDNA viruses that express their genomes in the nucleus use alternative splicing to encode multiple proteins. In contrast, poxviruses do not use alternative splicing because they replicate in the cytoplasm, where host splicing factors are not available Replicating in the cytoplasm necessitates virally encoded RNA polymerase, transcription factors, and DNA replication proteins, likely contributing to the large poxvirus genomes Two distinct infectious virus particles exists: - the intracellular mature virus (IMV) - the extracellular enveloped virus (EEV) IMV can acquire second double membrane from trans-Golgi, bud as EEV

What is recombination when it refers to RNA viruses?

Process of recombination that occurs in RNA viruses, - formation of chimeric molecules from parental genomes of mixed origin a. Co-infection of a cell by genetically distinct viral strains can lead to the generation of recombinant viruses. This process can occur in both non-segmented viruses or within a segment of a segmented virus. b. Co-infection of a cell by genetically distinct strains of a retrovirus can lead to the generation of 'heterozygous' virus particles, after which a template-switching event can lead to a recombinant provirus.

What are the effects of HIV-1 infection on lymphoid tissue

Progressive damage to lymph node germinal centres Connective tissue replaces much of the normal cell population End result is increased viremia and decreased immune capacity

How where protease inhibitors designed?

Protease Inhibitors were designed by modeling chemical structures to fit inside the catalytically active site of the HIV-1 protease, using the HIV-1 protease x-ray crystal structure HIV-1 protease is responsible for maturation of virus particles late in the replication cycle Cleaves gag and gag-pol polyproteins into functional protein subunits that form viral capsid Function as competitive inhibitors that bind directly to HIV-1 protease catalytically active site and subsequently prevent cleavage of polypeptides

What is Polyprotein processing, HIV?

Protease processes three separate polyproteins: Gag, Gag-Pol, Env Gag: MA, CA, NC Gag-Pol: MA, CA, NC, protease, RT and integrase Env: SU and TM

How can a proto-oncogene become an oncogene?

Proto-oncogenes encode normal cellular proteins that are growth factors, receptors, or signalling proteins in a growing network within the cell They can be activated to become oncogenes the end result is active cell division by genetic factors heredity); organic chemicals; radiation; and viruses There are many pathways affected by oncogenes and tumor suppressor proteins

What do Proto-oncogenes encode for?

Proto-oncogenes mainly encode components of growth factor signal transduction pathway - Mutated signal transducer molecules send incorrect "on" signals - Mutated transcription factors turn on genes at inappropriate times

How does Cytokine secretion induce an antiviral state?

RIG-1 detects the presence of viral dsRNA in a cell. The cell responds by secreting IFNα/β. IFNα/β binds to its receptor on nearby cells, inducing an antiviral state in them. The antiviral state prevents offspring virions from replicating.

What is the function of the distinct structure for positive sense RNA virus genomes?

RNA structures important for picornavirus replication - cloverleaf structure within 5' UTR, cis-responsive element within coding region, stem-loop structures within 3'UTR IRES-dependent translation initiation recruits translational machinery to an internal position in mRNA

How can viruses activate the cell cycle?

RNA tumour viruses - and their oncogenes - can activate growth signaling pathways DNA tumour viruses - and their tumour suppressor proteins - can disrupt pathways that prevent cell proliferation

What was the impact & discovery of reverse transcriptase(RT)?

RNA-dependent DNA-polymerase (or RT) - necessary for the replication of Retrovirus and Hepadnavoris genomes Changed molecular biology - central dogma (DNA > RNA > protein)

What is the Passive Immunity for Rabies prophylaxis

Rabies is a viral zoonotic disease spread to humans via bite of an infected animal Virus travels along nerves to reach central nervous system Delay between infection and arrival in CNS means post-exposure prophylaxis can prevent disease Most people with symptomatic Rabies do not survive Inactivated vaccine (killed virus) or rabies immunoglobulin are offered, depending on exposure or degree of risk

How do (-)RNA viruses provide a model for concerted nucleocapsid assembly?

Rabies virus (A) and Ebola virus have small (−) RNA genomes that are associated with nucleocapsid protein N, forming viral ribonuclear proteins (vRNPs) The nucleocapsid N protein is required during genome replication, and the new genomic RNA is encapsidated into RNP during RNA synthesis. Influenza is also a (−) RNA virus that assembles new helical influenza vRNP during RNA synthesis.

By what mechanisms do retroviruses transform cells?

Rapid tumour formation: eg. Rous Sarcoma Virus; 2 weeks - RSV has activated dominant oncogene in genome v-SRC) - Protein produced immediately when virus replicates Intermediate kinetics of tumour formation: eg, ALV; months - ALV carries no dominant v-ONC gene - Cis-activation: -- provirus turns on expression of endogenous oncogene Slow kinetics of tumour formation: eg. HTLV; years - HTLV carries no dominant v-ONC gene - Does not cause cis-activation of local oncogenes - A viral regulatory protein activates oncogenes by trans-activation

What are rashes a result of?

Rashes are produced when virions leave the blood, in many systemic viral infections - Macules (flat, small, non-elevated) and papules (small and swollen bumps on skin) develop when infection occurs in the dermis, with the lesion confined in or near the vascular bed. - Vesicles and pustules occur when the viruses spread from the capillaries to the superficial layers of skin Rash may also occur in mucosal tissue, such as those in mouth and throat - In measles infection vesicles of the mouth break down and become ulcers - such Koliks sports are diagnostics

What turns off cell proliferation?

Rb shuts off cell proliferation by binding to E2F (a transcription factor) - Undesirable condition e.g. low nutrients - pauses at Restriction point --no DNA synthesis, no cell division

How does host cell RIG-1 block HBV P protein?

Recognition of HBV by innate sensors in host liver cells triggers immune response that can eliminate virus The innate immune system RIG-1 sensor recognizes 5' ⍷ region of HBV pre genomic RNA (pgRNA) Virus replication is suppressed

What is the Hepatitis B live cycle

Relaxed circular DNA (RC-DNA) → covalently closed circular DNA (cccDNA) DNA is transcribed by host RNA polymerase into pregenomic RNA (pgRNA) and subgenomic mRNAs pgRNA is encapsidated, together with the P protein, and reverse transcribed inside the nucleocapsid (+)DNA synthesis from the (-)DNA template generates new RC-DNA

Where do positive strand RNA viruses replicate?

Replicate in the cytoplasm Positive or plus (+)strand RNA viruses have genomes that are functional mRNAs; may be capped and polyadenylated Host cell ribosomes assemble on viral genomes that have entered host cell, to synthesise viral proteins Earliest viral proteins are those needed to synthesise new genomes, and RdRp RdRp and other viral proteins needed for genome synthesis are encoded as a polyprotein that is cleaved by viral proteases Some viruses (flaviviruses, picornaviruses) - all viral proteins are included in polyprotein Other viruses (coronaviruses, togaviruses) synthesise a polyprotein that includes the RdRp; can synthesise more than one protein from a gene; also use subgenomic RNAs to encode structural and other proteins Viruses modify host cell membranes to construct viral replication scaffolds

What is the replication of SV40 genomes initiated by

Replication of SV40 genomes is initiated by large T antigen LT protein, T-Ag (the major early gene product of SV40) assembles at its binding site, ori Intrinsic 3'-5' helicase activity of LT unwinds DNA bi-directionally Viral DNA synthesis occurs in 5'-3' direction on both leading and lagging strands Copied genome is assembled in capsid Association of T-Ag with cellular p53 can be oncogenic

What is the resistance to CCR5 antagonist?

Resistance to CCR5 antagonist: Binding to CCR5 in the presence of Maraviroc Resistance to Maraviroc can occur when R5-tropic HIV-1 develops mutations that facilitate gp120-CCR5 binding Binding occurs despite Maraviroc attachment to CCR5, and conformational changes associated with receptor binding Emergence of preexisting minority variants of X4-tropic variants that are preferentially selected out from the use of CCR5 antagonist - Emergence of newly formed X4-tropic HIV as a result of mutation in HIV gp120. - This contrasts with emergence of preexisting minor variants of X4- tropic virus All patients must be tested for CCR5 tropism before initiating Maraviroc

What controls restriction point decision?

Restriction point decision is controlled by cellular protein Rb retinoblastoma protein): Rb is a tumour suppressor [if both copies of Rb are lost, retinal tumours of retinoblasts that form retina cause all retinoblasts to be lost by the age of 5] Oncogenic DNA viruses also the RNA virus (HCV) put cells into S phase by blocking Rb

What do retroviruses require for replication?

Retrovirus replication cycle requires integration into the chromosome

How do rodents play a role in animal-to-human transmission?

Rodents play critical roles in the introduction of new viruses into human populations in areas where these animals are abundant. Most hemorrhagic disease viruses, including Lassa, Junin, and the Sin Nombre virus, are endemic in rodents, their natural hosts. The viruses establish a persistent infection, and the rodents show few, if any, ill effects. However, substantial numbers of virus particles are excreted in urine, saliva, and faeces to maintain the virus in the rodent population. Humans become infected when they happen to come in contact with rodent excretions that contain infectious virus particles. infection by such rodent viruses can cause lethal outbreaks in humans as dead-end hosts.

What is the uncoating stages of Reovirus that leave virions partially inside the cytoplasm?

Rotavirus dsRNA is recognized by PRR, activating innate immune response Rotaviruses can evade the host innate immune response: mediated by viral NSP1 inhibition of NF-kB activation of transcription Reoviruses ( eg. Rotavirus) are unusual in that the infecting virion remains largely intact inside the host cell for all or some of the gene expression stages. Reoviruses have segmented dsRNA genomes enclosed by three layers of protein. The genome segments are surrounded by the inner capsid, a second a double-layered intermediate capsid particle, and third layer called the outer capsid. These naked viruses are internalized by endocytosis after which the outer capsid disassembles and the double-layered particle is present in the cytoplasm. The double-layered particle remains intact and serves as the first site of virus mRNA production, when enzymes in the core use the genomic RNA as a template to synthesize, cap, and tail viral mRNAs.

How can oncogenes occur in chicken?

Rous sarcoma virus RSV) of chickens contains oncogene v-src:an incorporated proto-oncogene c-src RSV is an altered form of Avian leukosis virus ALV), a virus that commonly infects chicken flocks src is a tyrosine kinase that is involved in regulation of cell growth and differentiation

What is the Rubella virus

Rubivirus genus; Metonaviridae family Mild childhood illness, rash may be present, similar to measles Rubella = 'German measles' Most cases occur in young adults Causes miscarriage or congenial rubella syndrome: serious birth defects in a baby if woman is infected while pregnant

What is Cytokine release syndrome?

SARS-CoV-2 binds to ACE2 receptors and infects cells. Viral replication & pyroptosis of the cell triggers release of damage associated molecules recognised y neighbouring cells. generate pro-inflammatory cytokines attract dendritic. Inflammatory cells damaged which releases cytokines which then recruit more inflammatory cells

What forces Host cell to express S phase genes, dsDNA viruses

SV40 forces the host cell to express S phase genes and uses large T antigen and host proteins for genome replication SV40 large T and small t antigens have multiple functions, including manipulation of the cell cycle and of apoptotic pathways Host cells susceptible to infection by SV40 are typically in G0 prior to infection, which means that they do not contain nuclear DNA replication proteins The virus must force the cell to express S phase genes in order to replicate its genome Changes in gene expression are accomplished by the early nonstructural proteins, large T antigen and small t antigen - Rb (retinoblastoma) protein pRb controls entry into S phase - Rb loss is associated with tumours: Rb is a tumour suppressor gene

What are features of effective vaccines?

Safe Protective Gives sustained protection Induces neutralizing antibody Induces protective T cells Practical considerations e.g. cost per dose, side effects

What are scaffolds and their importance for virus assembly?

Scaffolds are proteins that are needed for parts of the virus to assemble but are not found in the mature virion. Accurate assembly of some large icosahedral protein shells, such as those of adenoviruses and herpesviruses, is mediated by proteins that are not components of mature virus particles Among the best characterized is the precursor of the herpes simplex virus 1 VP22a protein

What is Influenza A?

Seasonal and pandemic influenza - Currently circulating human IVA strains are H1N1 and H3N2 IVA strains defined by combination of H and N proteins - 18 H subtypes (H1-H18) and 11 N subtypes (N1-N11); variants arise via reassortment of segmented genome (antigenic shift) and by point mutation (antigenic drift) Viruses infect animals, especially birds, pigs and humans - Occasional avian IVA transmission to humans

What is the Hepatitis C virus HCV replication cycle, RNA replication?

Several HCV proteins, likely in conjunction with host factors, induce rearrangement of the host intracellular membranes to create in the cytoplasm micro-environment, called the "membranous web" derived from the endoplasmic reticulum. Together, NS3/4A, NS4B, NS5A, and NS5B constitute the viral proteins of the replication complex, which replicates the positive sense RNA genome through a negative strand intermediate. The viral RNA-dependent RNA polymerase NS5B is the key enzyme of RNA synthesis. Newly synthesised RNA genomes are translated to produce new viral proteins, serve as new/additional RNA templates for further RNA replication and are progressively assembled to form infectious virions.

What is the pathogenesis of Chikungunya?

Short incubation - symptoms appear between 4 and 7 days after infection Most common symptoms of infection are fever and severe, debilitating joint pain Arthralgia can last for months and disease can evolve to chronic rheumatoid arthritis Serious complications include: neurological, cardiac and GIT problems in older patients; and meningoencephalitis in neonates There is no cure and treatment is focused on relieving the symptoms Disease onset coincides with rising viral titre, which triggers the activation of an innate immune response, the hallmark of which is the production of type I IFN

What is the replication of SV40 genomes?

Six large T antigen proteins form a hexamer, two hexamers bind ori in a head-to-head arrangement The hexamers have helicase activity that facilitates melting of the DNA at the ori DNA replication then proceeds bidirectionally, with each large T antigen hexamer progressing in opposite directions around the template in a process known as θ replication A. Large T antigen binds to ori using helicase activity to form two replication forks that will proceed bidirectionally around the genome in θ replication. (B) Crystal structure of a hexamer is composed of large T antigen helicase domains and six Zn2+ atoms (green)

How does virus entry occur via skin?

Skin of most animals is a barrier against viral infection, dead outer layer cannot support viral replication Entry through skin mostly occurs when integrity has been breached by breaks or punctures: - Mechanical transmission eg. (1) by insect vectors such as arthropods, introducing virus into highly vascularized ermis (2) by hypodermic needle punture into tissues below dermis. Urogenital tract mucosal cells are protected by mucous + low pH Minute abrasions allow viruses to enter - may produce local lesions, spread to other organs

What is the translation preinitiation complex and viruses that inhibit its formation?

Some viruses encode proteases that cleave one of the translation preinitiation complex subunits, marked with Xs. Examples include poliovirus and HIV, which both cleave PABP and eIF4G. Other viruses make proteins that bind to one of the subunits, sequestering it from participating in the 48S complex. An e.gis rubella virus (a togavirus), which sequesters PABP.

What is the Coevolution of the SIV capsid and the host restriction factor TRIM5 in monkeys?

Species-specific SIV strains infect non-human primates. The TRIM5 restriction factor in each host species blocks replication of most SIV. Only SIV strains that have adapted to overcome their host's TRIM5 protein can replicate. After a lentiviral capsid enters the cytoplasm, TRIM5 binds to the capsid and blocks subsequent steps of viral replication such as reverse transcription or transport of the cDNA to the nucleus, thus preventing infection Humans express a TRIM5α orthologue which only weakly restricts HIV-1

What is the composition of hepatitis B serum?

Subviral particles (SVP) are present at much higher concentration than viral particles (VP) in serum Contain only envelope glycoproteins and host-derived lipids, and it is not a complete virion - thus non-infectious Biological function of SVP is not fully understood - may be involved in antibody neutralisation (decoy) and impairment of host immune responses

What are the 3 requirements to ensure successful infection of host?

Sufficient virions available to initiate infection Cells at site of infection need to be physically accessible to virions, must be susceptible (bear receptors for entry), and permissive (contain intracellular gene products needed for viral replication) Local host antiviral defense systems must be absent or initially ineffective

What are dead end hosts?

Susceptible hosts that do not develop sufficient levels of virus in the blood to transmit the virus back to the arthropod for onward transmission dead-end hosts contribute little to the spread of the natural infection, but they may suffer from serious, life-threatening diseases. another species of biting insect (e.g., other mosquito species) can feed on an infected individual (bird, horse, or human) and then transmit the infection to another species not targeted by the original mosquito vector.

What is herd immunity

Susceptible individuals are - not immunized - cannot be immunized - vaccine did not induce immunity or has waned

What the server infection of dengue?

Symptomatic infection can be flu-like illness (dengue fever) or more severe illness with haemorrhagic manifestations and vascular leakage resulting in hypovolemic shock - previously known as dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS) - now known as severe dengue Time of onset of severe illness coincides with end of viraemic period: suggest an immunopathogenic basis Severe disease frequently occurs in the setting of secondary infection with heterologous serotype* Immunity to infection with one serotype is thought to be life-long Dengue vaccine licenced and available in some countries*

What is the Hepatitis C virus genome?

The HCV RNA (genome) consists of a single-stranded, positive-sense RNA approximately 9,600 nucleotide bases in length. The HCV genome contains a single, long, open reading frame (3,006-3037 codons) flanked by 5' and 3' untranslated regions (UTRs). The HCV RNA genome is used both for translation and transcription. The 5' region, which is upstream from the open reading frame, is approximately 340 nucleotides long and contains the internal ribosomal entry site (IRES).

What do HPV E6 & E7 do

The HPV E6 and E7 proteins prevent apoptosis and bind to pRB, causing expression of S phase genes The E6 protein covalently modifies the p53 protein, targeting it for degradation. The effect is to prevent apoptosis. The E7 protein binds to pRB, which prevents it from interacting with E2F transcription factors. The effect is to increase expression of S phase genes.

What is the evolving sugar "shield" of human immunodeficiency virus type 1?

The SU (gp120) subunit of the HIV-1 Env protein carries a large number of oligosaccharide chains, which form a dense shell that masks much of the protein's surface The sugar chains are highly ordered, forming the outer surface of the Env spike These oligosaccharides govern several properties of HIV-1. For e.g. , the tropism of the virus for CCR5 or CXCR4 coreceptors correlates with specific patterns of glycosylation in the variable loops of the SU subunit A major function of such modification is to block access of host anti-HIV-1 antibodies to SU protein epitopes Several observations have led to the hypothesis that HIV-1 carries an evolving carbohydrate "shield" that enhances immune evasion - for e.g. , the number of N-linked oligosaccharides added to SU tends to increase during the course of an HIV-1 infection, and the sites of N-linked glycosylation also change. Broadly neutralizing antibodies that inhibit reproduction of multiple strains and clades of the virus recognize mannose-containing glycans, in some cases in conjunction with a protein epitope.

What is the T-cell receptor?

The TCR includes many polypeptides including a dimer of the polypeptides α and TCR β chains A variable region at the distal portion of the TCR is the site for epitope binding (A) The TCR in a TH cell works with CD4; TH cells are also known as CD4+ T cells (B) The TCR in a CTL works with CD8; CTLs are also known as CD8+ T cells.

What are the disease syndromes of flavivirus infection?

The clinical presentation of ranges from asymptomatic infection to severe & life-threatening disease Individual flavivirus infections fall into two broad categories, visceral and neurotropic, although some have features of both Variability in disease presentation among individual flaviviruses reflects the interplay between the direct pathogenic effects of virus infection and injury caused by the requisite host response.

What is the Viral evasion of NET?

The cytokine IL-10 suppresses NET formation - Some viruses stimulate infected cells to produce IL-10 - Some viruses encode IL-10 homologs Some viruses produce their own DNAses, these may degrade the DNA component of NET (similar to bacteria)

What is the geneic evolution of the H7N9 virus in china?

The eight genes of the H7N9 virus are closely related to avian influenza viruses found in domestic ducks, wild birds and domestic poultry in Asia. The virus likely emerged via reassortment, where two or more influenza viruses co-infect a single host and exchange genes

What are HIV prevention strategies

The elusive HIV vaccine - T-cell mediated response - Neutralising antibody response: Induce antibodies that block HIV in the blood, preventing HIV from infecting the body cells. - Non-neutralising antibody response: Induce antibodies that recognise HIV and recruit other immune cells to help destroy the virus. Combination responses Numerous broadly neutralising antibodies have been identified and are being developed to target conserved regions of the HIV envelope - Many of these antibodies can neutralise as much as 90% of HIV strain

What are virus receptors and coreceptors

The first cell surface molecule that is found to be essential for virus binding is called its receptor. Sometimes, such binding is not sufficient for entry into the cell. When binding to another cell surface molecule is needed, that protein is called a coreceptor. e.g. HIV binds to cells via a receptor, CD4, and then requires interaction with a second cell surface protein, either CXCR4 or CCR5, the coreceptor.

What is the Concerted Assembly of Influenza virus ribonucleoproteins (RNPs)

The first stage of influenza assembly is for the PA, PB1, PB2, and NP proteins to form vRNP on new negative strands of RNA through concerted assembly For influenza virus, vRNPs arise from cRNP templates and the genomic vRNPs are packaged into helical structures during genome synthesis vRNPs must be packaged selectively with viral envelope, not cRNPs This is dependent on interactions with PA, PB1, and PB2 and the two RNA molecules These interactions mean vRNP are competent for export out of the nucleus, whereas cRNPs are retained in the nucleus Once exported, sequences near the 5ʹ and 3ʹ ends of the virus genome, which are conserved in all eight genome segments, target the vRNPs for packaging vRNP = viral ribonuclear protein cRNP = copy ribonuclear protein

What is flavivirus, replication cycle?

The flavivirus genomic RNA encodes a single open reading frame flanked by highly structured untranslated regions (UTR) that coordinate viral translation, replication and regulation of the innate immune response Virions are internalized by clathrin-dependent mechanisms that usurp host factors involved in the uptake of large macromolecules Viral RNA replication occurs on membranes of the host reorganized through the actions of the non-structural proteins. These virus-induced membrane structures spatially coordinate viral genomic RNA replication and virion morphogenesis, and shield replication products from host innate immune sensors. Virus particles assemble at and bud into the ER and traffic out of the cell

What is the genome of an RNA virus poluation cluster

The genome of an RNA virus population clusters around a consensus or average sequence A rare genome with a particular mutation may survive a selection event, and the mutation will then be found in all progeny genomes SD61G mutation emerged in eastern China, it is now global - No association with disease severity - No effect on neutralisation

What are Consequences of activating a naive CD4+ cell?

The goal of activating B cells during a viral infection is to make antibodies that bind selectively and tightly to viral antigens B cells use the B-cell receptor (BCR) to recognize epitopes; the BCR is a transmembrane form of the antibodies secreted by an activated B cell When an activated TH cell interacts with a B cell, the viral peptide is presented to the CD4+ T cell TCR in the context of MHC-II If the B-cell recognizes that epitope, the B cell will proliferate and its offspring will differentiate into antibody-producing plasma cells and memory cells

What is a Hepatitis B infection?

The incubation period is 45 to 180 days Can cause acute and chronic disease - Most acute infections are asymptomatic, and the virus is cleared from the host by immune response - Approximately 10% of infections are not cleared and the virus continue to replicate → chronic carriers (continued HBV viraemia 6 months after infection)

How is influenza an example of viral genome, antigenome and mRNA

The influenza virus is used as an example. The segmented viral genome is made up of (−) RNA (segment 5 in the figure). Antigenomes are perfect copies of the (−) RNA genome, lacking the 5ʹ cap and polyadenylation found in mRNA. Synthesis of antigenomes and genomes is indicated by the red arrows. The mRNA is a copy of the information in the genome, but it is also capped and polyadenylated; its synthesis is indicated by the black arrow.

What is the Co-Evolution of HIV Transmitted-Founder Virus and Evolving Neutralizing Antibodies?

The initial transmission event of sexually transmitted HIV-1 is mediated by one transmitted founder (TF) virus. The TF virus induces an initial antibody response, called the autologous neutralizing antibody, that is specific for the TF virus. The autologous neutralizing antibody neutralizes the TF but rapidly selects virus escape mutants, which in turn induces new antibody specificities. This process is repeated throughout virus evolution such that after years of infection, a spectrum of cross-reactive neutralizing antibodies are induced, with ~20% of chronically infected individuals making high levels of broadly reactive neutralizing antibodies.

What is the Transmitted Founder Virus?

The majority (∼70%) of HIV-1 infections worldwide result from heterosexual contact, which in the absence of confounding risk factors (e.g., genital ulceration), is generally an inefficient process. This is reflected in a mucosal bottleneck that reduces the genetic diversity of the HIV-1 quasispecies in the transmitting donor to only one or very few variants that seed the recipient

What are the oncogenic properties of HTLV-1 caused by?

The oncogenic properties of HTLV-1 are caused by two proteins, Tax and HBZ, encoded in the provirus HTLV-1 tax is a transcription regulator, whereas HBZ is also regulatory in nature; neither one has a known homolog among normal cellular genes. In addition to activating viral genes, Tax also activates many host genes, including those that promote host cell proliferation and resistance to apoptosis. HBZ has similar effects on host cells and may use multiple mechanisms to cause them. It can interact with pRB, thereby promoting cell cycling. Tax may be essential for starting the process of oncogenesis, whereas HBZ may be responsible for maintaining it, because although the two proteins have similar effects on host cells, they appear to be active at different times over the course of persistent oncogenic infections

What is Human papillomavirus (HPV)

The papillomavirus lytic reproduction cycle causes warts, including genital warts; additionally, human papillomaviruses are the leading cause of cervical cancer The gynecological exam procedure known as a pap smear is used to detect papillomavirus activity in cervical tissue in order to diagnose cervical cancer; vaccines such as Gardasil prevent the most common forms of cervical cancer by immunizing the population (including males) against human papillomavirus (HPV) HPV: spherical virions with circular dsDNA genome 6-8.5 kbp

What is the replication cycle of papillomavirus closely tied to?

The papillomavirus replication cycle is tied closely to the differentiation status of its host cell Papillomaviruses obligatorily infect stratified squamous epithelia, such as that found in human skin Papillomavirus can only infect the living basal cell layer, meaning that an injury is necessary to allow the virion to bypass the upper layers of the epithelium The earliest genes are expressed in the lower layers of the epithelium, whereas the later genes are expressed in the more distal layer

How does host cell surface influence virus ability to attach, penetrate and uncoat?

The plasma membrane of every mammalian cell type is composed of a similar phospholipid/glycolipid bilayer different sets of membrane proteins and lipids allow the cells of different tissues to carry out their specialized functions. The lipid bilayer is constructed from molecules that possess both hydrophilic and hydrophobic portions Membrane proteins are classified into two broad categories, integral membrane proteins and indirectly anchored proteins. The external portions of membrane proteins are decorated by complex or branched carbohydrate chains linked to the peptide backbone Such membrane glycoproteins quite frequently serve as viral receptors.

What is the structure of reverse transcriptase?

The retrovirus RT enzyme consists of two major domains: p66 and p51. Two active sites: - The polymerase active site - The RNase H active site RNase H binds to RNA in duplex (either RNA:RNA or RNA:DNA) and makes internal cleavages to break apart RNA template This activity is essential in the synthesis of complementary dsDNA

What are the risk groups for Hepatitis B infection?

The risk for chronic infection varies according to the age at infection and is greatest among young children HBV infection in a pregnant woman poses a serious risk to her infant at birth Perinatal HBV transmission can be prevented by identifying HBV-infected pregnant women and providing hepatitis B immune globulin and hepatitis B vaccine to their infants within 12 hours of birth

What is the pathway of virus particle assembly and release

The structural units that are often the first assembly intermediates are the homo- or hetero-oligomers of viral structural proteins from which virus particles are built Packaging of the genome can be coordinated with assembly of the capsid or nucleocapsid, and for enveloped viruses, the assembly of internal components can be coordinated with acquisition of the envelope. - Reactions common to all viruses are shown in yellow, and those common to many viruses are shown in blue. - The arrows indicate a general sequence that applies to only some viruses

What is the influenza tissue trophism?

The trachea and bronchioles are much easier to reach than the alveoli for aerial-transmitted virus Human influenza viruses preferentially bind to host glycoproteins/glycolipids containing sialic acids in alpha 2,6 linkage, whereas avian influenza viruses bind to those containing sialic acids in alpha 2,3 linkage Human trachea and alveoli epithelial cells mainly express alpha 2,6 sialic acids, when only alveoli express alpha 2,3 sialic acids explains why avian viruses could successfully infect humans only when breathed at high doses

What is the Alphavirus replication cycle?

The virus binds to a host receptor via the E1 and E2 glycoproteins. The virus is endocytosed in a clathrin-dependent manner. Nonstructural proteins are translated first from the full-length viral RNA, allowing assembly of the viral replication complex. The structural proteins are translated from the subgenomic RNA. The capsid protein assembles into NCs with the full-length viral RNA. pE2, 6K and E1 insert into the endoplasmic reticulum membrane and transit to the host plasma membrane via the secretory pathway.

How are long terminal repeats(LTR) essential for transcription,HIV?

There are many sequences in the HIV-1 LTR that interact with host transcription factors Core promoter of HIV-1 in the LTR is composed of a TATA box & many transcription binding sites The enhancer region of the LTR contains binding sites for other transcription factors The 4' and 3' LTR are identical, but serve different functions The 3' LTR regulates 3'-end processing of the pre-mRNA affecting polyadenylation and transcription termination

What is the Viral evasion of T cell response?

There are viral proteins that are difficult to process into epitopes so that they are never loaded onto the MHC-I for display - e.g. EBNA1 protein from Epstein-Barr virus expressed abundantly in cells harbouring a latent EBV infection. The protein is resistant to degradation by the proteasome, reducing viral epitope display in MHC-I - occupying the proteasome unproductively, the evasion mechanism reduces MHC-I display of all endogenous antigens. If the proteasome functions normally and produces potential epitope peptides, those peptides must be transported into the lumen of the ER through the transporter TAP so that they can associate with the MHC-I in the ER. - Several different herpesviruses encode proteins that block the function of TAP so that viral epitopes never enter the lumen of the ER. - e.g. herpesviruses target the MHC-I-epitope complex to the lysosome where the complex is degraded without ever reaching the plasma membrane. - herpesvirus varicella zoster virus (VZV) causes the MHC-I-peptide complexes to accumulate in the Golgi apparatus

What are the liver, Spleen, Bone Marrow and Adrenal glands characterised as?

These organs are characterized by sinusoids, lined with macrophages Macrophages are often infected by viruses present in blood underlying cells then infected Eg. Viruses in blood infect Kupfer cells, the macrophages, that line liver sinusoids.

How do viruses enter an intact nucleus?

They must manipulate gated nuclear pores All eukaryotic RNA viruses except orthomyxoviruses (influenza) and retroviruses (HIV) express and replicate their genomes in the cytoplasm, whereas all eukaryotic DNA viruses except poxviruses (vaccinia and variola) express and replicate their genomes in the nucleus Eukaryotic cells have a complex nuclear envelope defining the boundaries of the nucleus. The nuclear envelope has two lipid bilayers; the outer layer is contiguous with the endoplasmic reticulum. Macromolecules enter the nucleus through gated structures called nuclear pore complexes. The overall structure of a nuclear pore complex is that of a ring with filaments that extend toward the cytoplasm, and a basket structure that extends into the nucleus Large molecules such as virus genomes require active transport through the nuclear pore complex. Transport through nuclear pores requires a nuclear localization signal.

what is does quasispecies refer to?

This phenomenon has led to the realization that RNA virus populations are quasispecies, or mixtures of many different genome sequences. RNA polymerases lack 3' exonuclease proofreading activity - average error frequency for 1 in 104-105 nucleotides polymerised Mutations accumulate during replication and recombination - all RNA viruses exits as mixtures of genetic variants, or quasispecies Reverse transcriptase (RT) lacks 3' exonuclease activity and retroviruses mutate & evolve at rates similar to those of non-reverse transcribing RNA viruses Retroviruses also exist as quasispecies Most mutations have no effect/ result in viruses that are not able to replicate, but certain mutations result in viruses able to: - Successfully evade the immune system; - Develop drug resistance; - Thwart vaccination strategies

How must mRNA in eukaryotic cell be processed prior to translation on ribosomes

Three main processing steps: - Capping at 5' end - Addition of a polyA tail at 3' end - Splicing to remove introns Virus genomes must mimic mRNA to be translated May not have the exact features of mRNA but must compensate for lacking elements

What is the time course Dengue virus infection?

Time course of acute infection and immune responses during symptomatic dengue virus infection Peak viraemia correlates with high fever and coincides with the initiation of IgM and IgG production, which promote clearance of virus infection. During secondary heterologous DENV infection, the period of viraemia is shorter, likely owing to cross-reactive immunity, including pre-existing antibodies. Cross-reactive memory T cells promote an earlier and potentially stronger T cell responses than that seen during primary infection - the risk of severe dengue is higher in patients who experience secondary heterologous DENV infection

What are host determinants for contagiousness individual level?

Tissue and cellular tropism - viral shedding at different sites e.g. nose, throat Symptom presentation - presymptomatic, asymptomatic or symptomatic transmission Lung function - exhaled particle number and size distribution Pre-existing immunity from prior vaccination - heterogeneity in viral shedding e.g. supershedder

What are host determinants for susceptibility at individual level?

Tissue-specific receptor expression, glycosylation and glycan expression - site of infection - risk of infection Pre-existing immunity from prior infection or vaccination - risk of infection Lung anatomy - site of virus-laden particle deposition

Why is the HIV-1 accessory protein TAT essential for viral gene expression

Transcription initiation is not sufficient to produce mRNA for transcription, elongation, involving host pol II must also occur. The HIV-1 accessory protein, Tat, promotes elongation through interaction with a stem-loop structure called the Tar element, found in all HIV-1 mRNA When the Tar element binds to Tat, the whole complex then binds to host proteins including a kinase. The kinase phosphorylates Pol II which promotes elongation

What are Transformed cancerous cells

Transformed cancerous cells grow on top of each other instead of responding to contact inhibition as normal cells would.

What are the effects of normal nells being transformed in an uncontrolled manner?

Transformed cells are immortal: they grow indefinitely eg. Vero; HeLa) Loss of contact inhibition Loss of anchorage dependence Form colonies in semi=solid media Altered requirement for growth factors and nutrients Transformed cells are not necessarily oncogenic ie. may not become cancerous

Where does does translation of mRNA occur

Translation of mRNA occurs at eIF4G initiation complex The mRNA is recruited to the eIF4F complex across the interaction of the 3;end and polyA- binding protein (PABP), and the 5' cap and eIF4E Complex scans the 5' UTR to reach AUG Note: Cap-dependent translation initiation requires a large number of protein factors that act in a stepwise assembly process Internal ribosome entry sites (IRES) are cis-acting RNAs that can directly recruit and activate the ribosome

What is the Enterovirus infections of CNS?

Transmission occur via hand-to-mouth contact (saliva, nasal mucous or sputum of infected person) Similar to poliovirus in epidemiological and infectious characteristics but less virulent Responsible for respiratory infections, conjunctivitis and hand-foot-mouth disease (HFMD) Rare cases of coxsackievirus and echovirus paralysis, aseptic meningitis and encephalitis Enterovirus 71 - Usually causes mild disease in adults and children - Outbreaks of EV71 are associated with severe disease - meningitis and encephalitis - especially in young children (under 5 years) - Reported in Asia for many years and occasionally in Australia

What are the methods off virus transmission

Transmission: the spread of virus from one susceptible host to another Two patterns: - E.g. Measles and HAV are maintained solely in humans. Humans are the reservoir of infection Alternate infection of insect and vertebrate hosts E.g. Rabies virus is transmitted from animal to human but is maintained in animal cycles. Dengue virus is transmitted and maintained in the vector-to-human cycle Viral diseases shared by humans and animals or insects are called zoonoses

What does tumour suppressor gene mean?

Tumor Suppressor gene: "Loss of function" A gene whose normal activity prevents formation of a cancer. Loss of this function by mutation enhance the likelihood that a cell can become cancerous a normal process to maintain control of cell division is lost.

What is the process of transcription in Hepadnaviruses, Hepatitis B Virus (HBV)?

Uncoating and release of viral genome occurs within the nucleus (1), where host enzymes convert it to covalently closed circular DNA (cccDNA)(2). Transcription (3) produces mRNA that is exported to the cytoplasm and translated (4). Long pregenomic RNA (pgRNA) is exported but not translated (5) and encapsidated (6). pgRNA is reverse transcribed within the viral particle (7). Viral particles containing genomic DNA can be trafficked into the nucleus for cccDNA synthesis, amplified, and used to sequence more mRNA (9 t 11), or can me trafficked to a membrane to be processed for assembly

How do Viruses modify internal membranes in order to create virus replication compartments (VRC)

VRCs are assembled by nonstructural viral proteins, viral genomes, host lipids, and host proteins VRCs typically appear as invaginations of membranes associated with various organelles such as mitochondria, ER, Golgi, plasma membrane The interior of the VRC is connect to the cytoplasm and serves as the exit point for viral mRNA

what is does fidelity refer to?

Various RNA viruses' RNA-dependent RNA polymerases differ in their fidelity: how accurately they copy viral genomic RNA.

What is the global burden of viral cancers?

Viral Cancers account for approximately 20% of human cancers - Major cause of liver and cervical cancer in humans - Malignancy is not required for viral replication - Cancer is side effect of host response or host-viral interaction

What does Viral assembly refer to?

Viral assembly refers to: specifically to the assembly of capsids with genomes and so is universal to all viruses. Enveloped viruses must also acquire a membrane during assembly

What is the localization of viral proteins to the plasma membrane

Viral envelope glycoproteins (red) are cotranslationally translocated into the ER lumen and folded and assembled within that compartment. They travel via transport vesicles to and through the Golgi apparatus and then to the plasma membrane. The internal proteins of the virus particle (blue) and the genome (green) are also directed to plasma membrane sites of assembly

What is the Viral evasion of MHC-II presentation?

Viral evasion strategies (red) include: - reduction of transcription of MHC-II genes (1) - degradation of MHC-II proteins in the ER (2 - targeting the MHC-II from the Golgi body to lysosomes where the MHC-II will be degraded (3) - blocking processed epitopes from reaching MHC-II-containing secretory vesicles (4)

What is the Integron of HIV cDNA using viral integrase?

Viral gene expression can't occur until the viral DNA becomes inserted into a host chromosome. Catalysed by the viral integrase enzyme - pre-packaged within the virion

What do viral genomes not encode for?

Viral genomes do not encode for complete protein synthesis (e.g. ribosomal RNA), proteins of energy metabolism or membrane biosynthesis, telomers or centromeres

What do viral genomes encode for?

Viral genomes encode some, but never all, of the proteins required to complete for viral replication

What is an Overview of the innate and adaptive immune response to viruses?

Viral infection prevented by type I interferons and neutralizing antibodies Infected cells are eliminated by NK cells and CTLs

How is infectiousness of a virus determined?

Viral infectiousness is quantified and viruses are asigned a reproduction number (Ro) Ro - average number of secondary cases generated by one primary case in a susceptible communit (with no control measures) The higher the Ro value, the more persons can be infection from one case However, the incubation period in the host (and the vector where relevant) is also important - Viruses with high Ro and short incubation periods are significant public health problems eg. Influenza - Viruses with longer incubation periods and low Ro gives time for possible use of quarantine to stop an outbreak eg. SARS

What are the Viral origins of replication

Viral origins of replication are AT-rich DNA sequence segments recognized by viral origin recognition proteins Viral genomes may have up to 3 ori

What is Viral Pathogenesis?

Viral pathogenesis the process that occurs when a virus infects a host - is the integrated result of many complex factors unique to a particular virus, a particular species, and an individual host The interplay of these factors determines the nature of the infection, - whether disease occurs, - and the severity of disease Individual factors involved in pathogenesis can be studied in detail, but all conclusions derived from reductionist experiments utilizing molecular and biochemical approaches need to be validated in living organisms

What is the Acquisition of envelope by influenza virus, and virus budding?

Viral proteins are synthesized in the cytoplasm and on the endoplasmic reticulum. Viral proteins that will become part of new vRNPs must be trafficked to the nucleus (black arrows) while the viral envelope proteins traffic to the plasma membrane (red arrows). New vRNPs are synthesized in the nucleus and are then exported to the cytoplasm. They travel along the microtubule network at the periphery of the cell, bundling along the way. Eight different vRNPs gather under a patch of plasma membrane containing matrix and spike proteins. The new virion buds away from the surface of the host cell.

What is the Pseudodiploid nature of retroviral virions?

Virions that package two genetically distinct copies of viral gRNA (red and blue lines) have the potential to generate recombinant proviruses if one or more recombinogenic template switches (indicated with a dashed black line) occur during reverse transcription. Despite co-packaging of two gRNAs, retroviruses are not truly diploid because only one allele at each locus is preserved in the integrated provirus, and any progeny produced from a cell harbouring a single recombinant provirus will transmit only one allele at each locus in its progeny.

What is Virologic rebound?

Virologic rebound suggests emergence of drug resistant virus variants Virologic rebound is defined as confirmed detectable HIV RNA (greater than 200 copies/mL plasma) after virologic suppression Drug resistance should be assessed

What is the Baltimore classification?

Virus are categorised based on the type of nucleic acid genome and replication strategy All viruses must produce mRNA that can be translated by cellular ribosomes to produce viral structural protein Knowledge of strand polarity informs the steps to initiate replication and expression of the viral genome

How are Host cell cytoskeleton and membranes are important during virus assembly?

Virus assembly occurs by interactions between the viral structural proteins and the viral genome. In many cases the virus proteins must still interact with specific host membranes in order to complete assembly. In eukaryotic viruses, assembly factories known as virus replication complexes (VRC) contain viral genomes, viral RNA polymerases, and other nonstructural proteins, and may be fashioned from the membranes of the ER, Golgi, or other cytoplasmic organelles or from lipid droplets

What is Viral Spread?

Virus infects target cell at site of entry Progeny viruses may remain localized: is contained within epithelium by immune response and by physical structure of tissue Some viruses are disseminated: spread beyond primary site Systemic infection: many organs are infected

What is the naming scheme/taxonomic categories for viruses

Virus naming schemes are not systematic and can seem whimsical. Viruses can be named for: the diseases they cause. e.g. polio & influenza virus symptoms of the diseases they cause, e.g. Crimean-Congo hemorrhagic fever virus. the parts of the human body they infect, e.g. common cold virus rhinovirus (rhino = nose in Greek) or hepatitis (liver in greek). the geographical location where they first emerged, e.g.as Marburg virus and Ebola virus. the properties of their virions. e.g., the picornaviruses are tiny (pico) and have RNA genomes, whereas the geminiviruses have twin capsids (gemini is Latin for twins). Coronaviruses seem to have 'crowns' in EM images. Obvious evolutionary relatedness does exist among some viruses, so they may be classified by order (-virales), family (-viridae), subfamily (-virinae), genus (-virus) and species. Some viruses also have subspecie

How do cells infected by viruses exhibit morphological changes in addition to inclusion bodies?

Virus-induced morphological changes include - shrinking of the nucleus, - proliferation of cytoplasmic membranes, - proliferation of the nuclear membrane, - proliferation of cytoplasmic vacuoles, - formation of syncytia (cell-to-cell fusion) - rounding up and detachment of tissue culture cells Proliferation of membranes typically occurs when those membranes are needed to form viral replication compartments Syncytia typically occur when the fusion peptides of maturing enveloped viruses trigger fusion of neighbouring cell membranes before the assembly process can be completed to produce budding virions, or they may occur to benefit the virus by enabling cell-to-cell spread from the cytoplasm of an infected cell into a neighbouring cell following fusion Rounding up and detachment of tissue culture cells indicates cell death because healthy cells lie flat and are attached to the culture vessel:

How do viruses acquire envelopes?

Viruses acquire envelopes through one of two pathways Enveloped viruses express both soluble cytoplasmic proteins and transmembrane proteins, which are translated at different sites yet must come together. They acquire their membranous envelope at a site distinct from either the nucleus or the cytoplasm, where their offspring genomes accumulate Two strategies: A. Assembly of the capsid and genome occurs first. Acquisition of the envelope occurs next: the assembled capsid interacts with a cellular membrane that also contains virus spike proteins and pinches off; influenza virus uses this strategy. B. Formation of internal structures of the virion occur in coordination with the envelope eg. HIV

What are the 4 traits that defines viruses

Viruses are obligate intracellular parasites that have an infectious extracellular stage. - extracellular stage as a virion All viruses encode at least one capsomere protein. - Capsomeres cover and protect the nucleic acid in a virion. All viruses replicate, not by growing larger and dividing as do cells, but by assembly. - cells infected by viruses synthesize the component parts of the virion, and then the parts, once synthesized, spontaneously assemble into new virions. Viruses have the capacity to evolve. - Because the minimum composition of viruses is nucleic acids and protein units called capsomeres, viral populations can change through typical evolutionary processes that alter those nucleic acids in a heritable way.

How do viruses evade specific proteins expressed by ISG

Viruses can also evade the specific proteins expressed by ISGs. e.g. PKR is targeted by many viruses, using different mechanisms: - Vaccinia virus and reoviruses encode proteins that bind to dsRNA, sequestering it away from activating PKR - HepC, HSV-1 encode proteins that directly bind PKR preventing it from blocking translation - CMV interferes with the normal cytoplasmic localisation of PKR, causing it to accumulate in the nucleus where it can't block translation

How can via inactivation viruses cause transformation of suppressor p53?

Viruses cause transformation via inactivation of the tumour suppressor p53 p53 is a tumour suppressor: arrests the cell cycle in the presence of damaged DNA,and leads to apoptosis of cells whose DNA is irreversibly damaged Virus infection causes DNA damage and hypoxia - activates p53 Many viruses alter p53 activity

What strategies have viruses evolvedto block translation of host mRNA?

Viruses do not carry their own protein biosynthesis machinery and the translation of viral proteins, therefore, requires that the virus usurps the machinery of the host cell Regulated mRNA translation is a post-transcriptional mechanism that controls gene expression and directly and rapidly varies protein abundance Much of the regulation of this process focuses on the rate-limiting initiation step, which involves ribosome recruitment to mRNA The 48S translation preinitiation complex requires the poly(A) tail and the 5ʹ cap of the mRNA Viral proteases target one or more of the proteins in this translation initiation complex. By proteolytically degrading the initiation proteins, they are no longer available to the complex, and all translation initiation by the 48S complex is impeded Viruses that destroy translation initiation in these ways must have a way of bypassing the 48S complex for the purpose of translating their own mRNA. By far the most common solution to this problem is the use of an internal ribosome entry site, or IRES, in the viral mRNA transcripts

How can Viruses damage epithelial cells of respiratory tract?

Viruses enter and replicate in epithelial cells - extensive damage with influenza virus/less damage with rhinovirus Infected cells lyse, cause oedema - enables secondary bacterial infection - most IV-associated deaths arise from pneumonia or cardiac failure Severity of viral illnesses ranges from sore throat, nasal congestion to life-threatening pneumonia, bronchiolitis; exacerbations of asthma and chronic obstructive pulmonary disease (COPD)

How do viruses replicate?

Viruses replicate through a lytic replication cycle the host cell bursts open, or lyses. one-step growth cycle is a method to study virus replication in cells. conditions in which each cell is infected by a single virus, the initiation of infection is synchronous: - Adsorb virus onto cells - Dilute culture - Sample - Assay the number of extracellular viruses increases exponentially. Eventually the number of viruses levels off, and there is no further increase in the population size.

How does Cell-to-cell spread evades the neutralizing antibody response?

Viruses that spread from one cell into another without spending much time in the extracellular space cannot be neutralized by antibodies

How do DNA tumour viruses interfere with cell proliferation?

When stimulated to divide, cells enter the G1 phase and then enter S, where they replicate their DNA and prepare for cell division DNA viruses need cells in S phase so they can replicate their DNA

How can virus infecting affect cells?

When viruses infect these cells, the cells typically display a variety of cytopathic effects that depend on the specific host cell and virus. For example, many viruses cause infected cells to round up and detach from the tissue flask as they die (B).

Where did the coronavirus originate?

Wuhan, China

What is the live attenuated vaccine for yellow fever?

Yellow fever disease spectrum ranges from mild acute illness to total organ failure and death Yellow fever: case fatality rates > 20% YF vaccine YF17D was derived by passage through mice and other lab animals, >100 subcultures 48 nucleotide substitutions (of ~11,000 nt) of which 22 are non-synonymous, scattered throughout genome

What are zoonoses?

Zoonoses are infections of humans by viruses that pre-exist in stable relationships with nonhuman hosts. Most emerging viruses come from zoonotic infections

How is Viral Reverse Transcriptase is highly error-prone, HIV?

a. Each new virion encodes approximately one new mutation b. Viral recombination in CD4+T cells also generates HIV-1 genetic variation. When two HIV-1 virions with different genetic sequences enter the same cell, they can both integrate and produce viral RNA. Homologous recombination or packaging of different RNA from different parent viruses leads to creation of entirely new HIV-1 genomes Both mechanisms shown here contribute to HIV-1 genetic variability and therefore to the potential of the virus to escape host immune responses

What is Passive Immunity?

administration of antiserum containing preformed antibodies Immediate protection against recent infection or ongoing disease Limitations: can trigger hypersensitivity reaction ('serum sickness'); antibodies are degraded very quickly

How do viruses interract with host cell compoenents and processes in order to replicate?

any viral effects on host cells contribute substantially to the efficiency of viral replication and tip the balance in favour of the virus These effects include viral subversion of host transcription, translation, and replication related machinery In animal hosts specifically, viruses cause cytopathic effects (CPE), which are pathogenic changes in cellular structure associated with cell death or malfunction - CPE effects cause the cells to have an abnormal shape and to detach from their culture dish or extracellular matrix - Most of these effects are harmful and are caused when the virus interferes with a normal host process, such as translation, apoptosis, protein degradation, or autophagy - Proliferation of intracellular membranes is another typical structural change in infected cells; most often it occurs because the virus uses host membranes to create virus replication compartments (VRCs)

Can bacteriophages combine shapes

bacteriophages (C) combine icosahedral and helical elements, - their heads, full of nucleic acids, are icosahedral - their tails are helical assemblages of specialized tail proteins.

What is the Hepatitis C virus transmission and disease progression?

contact with blood from an infected person and sexual transmission (more often in MSM) Incubation period 2-6 months 80% of infected people are asymptomatic (rare early diagnosis) 70% of infections result in chronic persistent infection, leading to the development of cirrhosis in approximately 10-20% of patients over 20-30 years of HCV infection. slowly progressive disease characterised by persistent hepatic inflammation.

What is the second stage of virus binding & attachment?

irreversible binding to a specific receptor molecule on the host cells Shape complementarity is essential for attachment. The virus protein is bound to its cellular receptor through noncovalent intermolecular forces that are additively strong and can occur because of shape complementarity. Tight binding such as this is irreversible because it soon triggers the host cell to internalize the virus. Binding is irreversible because the consequences of irreversible attachment, which are penetration and uncoating, do not ever proceed backwards. Viral proteins interact closely and specifically with host cell receptor molecules for irreversible attachment to occur. The dissociation constant KD is a measure of the strength of interaction between two molecules (typically 1x10-9 or less). Binding affinity is the strength of the binding interaction between a single molecule and its ligand. When there are multiple interactions among two or more molecules (as is most often the case), the interaction between receptor and ligand is referred to as avidity: the collective strength of multiple noncovalent intermolecular forces during an interaction among macromolecules.

What is the most contagious infectious disease known?

measles

What is a virion?

metastable particle primed for uncoating once irreversible attachment and penetration have occurred Virions have two distinct roles: - to protect the virus genome during transmission - to release the virus genome into a host cell Virions are structurally biased toward protecting the genome until they engage irreversibly with a host receptor. The intermolecular interactions among the structural proteins of a virion, and between them and the genome, maintain the virion in its characteristic shape. Virions exist in this metastable state until a host cell triggers them to advance from attachment to the penetration and uncoating stage. Triggers from the host cell include binding to a cellular receptor, a decrease in endosomal pH, proteolytic degradation by a host enzyme, or some combination of these factors

How are there Selective pressures and constraints on viral evolution: Genome size versus mutation rate?

most mutations are neutral or detrimental viruses with larger genomes can tolerate only a low number of mutations in order to avoid creating multiple mutations in multiple genes and in each new genome viruses with smaller genomes can have a higher mutation frequency - will result in a low number of offspring with multiple mutations because the genome is smaller - Mutation rate is defined as number of substitutions per nucleotide per generation - Genome size is defined as nucleotides for single-stranded genomes and as base pairs for double-stranded genomes

can viral genomes be both DNA & RNA?

no, they must be either RNA or DNA never both

What does case-fatality ratio mean?

number of deaths divided by the number of individuals with illness

What does morbidity mean?

number of individuals who became ill divided by the number of infected individuals

What is multiplicity of infection?

number of infectious particles added per cell Amount of virus (plaque forming units, PFU) divided by number of cells - PFU/# cells e.g.Infection depends on random collision of virus particles and cells When susceptible cells are mixed with virus, some cells are not infected, other cells receive 1 or more virus particles - best represented by the Poisson distribution

What does incidence mean?

number of people infected divided by the population

Define Viremia

presence of infectious virus in blood [virions may be free in blood or contained within infected cells, such as lymphocytes]

What is Variolation?

pus taken from a smallpox blister and introduced into skin of an uninfected person to confer protection

What is the host receptor for influenza

sialic acid, also known as neuraminic acid The HA(Haemagglutinin) protein of influenza A viruses that cause human infections bind preferentially to the form of α-2,6-linked sialic acid that is most common on nonciliated human respiratory cells. In contrast, the HA1protein of influenza A viruses that live in bird populations bind better to α-2,3-linked sialic acids that are common in birds. Avian influenza A cannot undergo person-to-person transmission until the HA knob evolves and acquires the right sequence and structure to bind preferentially to human respiratory epithelial α-2,6-linked sialic acids All human cells have a glycocalyx consisting of a variety of carbohydrates, as shown by staining of the sugars on the surface of this human respiratory tissue. Most animal viruses, like influenza, interact with glycosylated host receptors because essentially all surface-exposed host proteins are glycosylated

How do animal viruses translate proteins?

soluble proteins are translated by cytosolic ribosomes, whereas transmembrane proteins must be translated by ribosomes attached to the rough endoplasmic reticulum viruses use same system the host cells use to translate their own transmembrane proteins.

What are the 4 general types of interactions between virus and host?

stable, evolving, dead-end, and resistant: - Stable host-virus interactions are those in which both participants survive and reproduce. The hallmarks of the evolving host-virus interaction are instability and unpredictability. - The dead-end interaction, in which the virus is not transmitted to other members of the new host species, is a frequent outcome of cross-species infection - The resistant host interaction represents situations in which the host blocks infection completely

What are Adjuvants

substance added to vaccine to increase the body's immune response to the vaccine

What are resistant hosts?

there is no infection because host cells are not susceptible, not permissive, or the primary physical, intrinsic, and innate defences are so strong that most potential invaders are diverted or destroyed upon contact other cases, organisms may become infected and produce some virus particles, but the virus is cleared rapidly without activation of the host's acquired immune system This outcome contrasts with an inapparent infection, in which an immune response is mounted but the individual exhibits no signs of disease

What is the Influenza A virion structure

two surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA), and the M2 ion channel protein are embedded in the viral envelope, which is derived from the host's plasma membrane The ribonucleoprotein complex comprises a viral RNA segment associated with the nucleoprotein (NP) and three polymerase proteins (PA, PB1, and PB2) The matrix (M1) protein is associated with both ribonucleoprotein and the viral envelope

What is the Influenza A virus replication process?

vRNP components enter nucleus after uncoating (1). mRNA synthesis proceeds (2) and is exported to cytoplasm (3) Some proteins are translocated back into cytoplasm (5) where genome is used to synthesize many antigenomes (6) (antigenomes in a complex with NP are called cRNP) and new genomes (7) New genomes can be used to make more mRNA (8) New vRNPs are exported to the cytoplasm for assembly and maturation, new virions exist host cell through budding

What is the final step in Influenza virus release?

viral NA(Neuraminidase) removes sialic acids from both cellular receptors and from newly synthesized HA and NA on nascent virions, which have been sialylated as part of the glycosylation processes within the host cell Panel A shows the action of neuraminidase in the continued replication of virions in influenza infection. The replication is blocked by neuraminidase inhibitors (Panel B), which prevent virions from being released from the surface of infected cells.

What are the patterns for viral infections?

viruses can also cause longer-term persistent infections. Persistent infections were once considered unusual, but but now indicated to be extremely common most adult people have at least one longterm infection caused by a member of the Herpesviridae family. During some chronic infections, viral replication is continual, though the immune system holds clinical disease in check. Latent infections are those in which there is little or no production of virions, yet the virus persists, typically as viral DNA in the nucleus of a differentiated cell, analogous to a prophage. Latent infections are typical of the Herpesviridae.

How do viruses produce proteins?

viruses must direct the synthesis of mRNA to produce proteins. No viral genome encodes a complete system for translating proteins; all viral protein synthesis is completely dependent upon the translational machinery of the cell.

Can viruses enter cells through phagocytosis?

yes, via macrophages, neutrophils that ingest viruses as part of immune response E.g. Herpesvirus A. Some viruses enter host cells through phagocytosis, which ultimately exposes the virion to the contents of a phagolysosome, triggering uncoating. B. Kaposi's sarcoma virus, formally known as human herpesvirus 8, is entering a cultured human fibroblast via phagocytosis.

What is DNA Replication with a Proofreading Polymerase?

Fidelity of DNA polymerase is the result of accurate replication of a desired template: - ability to read a template strand - select the appropriate nucleoside triphosphate - insert the correct nucleotide at the 3´ primer terminus - some DNA polymerases possess a 3´→5´ exonuclease activity: "proofreading" When the polymerase recognizes an error, the mismatched base is transferred to the exonuclease active site and the base is excised

How does v-src differ from c-src?

It lacks the regulatory tyrosine near the C-terminus, leading to constant activity and uncontrolled cell growth

What host range of a virus, and tissue tropism mean?

Host Range - Variety of different species that the virus can infect Tissue tropism - the different tissue or cell types that a virus infects once inside susceptible animal

What is the Chikungunya virus?

11.5kb enveloped (+) ssRNA Alphavirus genus, Togaviridae family Aedes (Ae.) mosquitos - Ae. africanus, Ae. aegypti and Ae. Albopictus - the latter after E1-A226V mutation - increase infectivity and transmissibility increased epidemic potential

How do capsids associate with genomes using Sequential Assembly?

During sequential assembly, regular groups of capsomers such as pentamers or hexamers assemble first and then assemble together to make a hollow shell or procapsid.

Define Passive Viremia

introduction of virions into blood without replication at site of entry

What is Active Immunity?

protection induced by person's own immune system, with specificity and memory, long term Both humoral and cell-mediated Antigens may be live attenuated; inactivated; subunit Inactivated/subunit/killed vaccines are optimized by addition of adjuvants. Usually require boosters

What do oncogenes code for?

proteins that potentially can transform a normal cell into a malignant cell. May be transmitted by a virus - (a viral oncogene)

What is the Viral evasion of Type I IFN

A: A poxvirus protein binds to type I interferon before the IFNα/β can bind to its cellular receptor. B: Two viruses (SARS, HepC) induce ubiquitination and subsequent proteolysis of the IFN receptor (reduces cell's ability to respond to IFN) C: Several viruses target STAT1 to the proteasome. D: Some virally encoded proteases degrade STAT2. E: Other viruses prevent JAK1 or TYK2 from phosphorylating the STATs (Marburg, HPV) F: Viral phosphatase can dephosphorylate STAT1, blocking dimerization with STAT2 (Vaccinia) G: Some viruses block transcription of ISGs by interfering with IRF9 activity (HPV, reovirus)

What is the preintegration complex?

After reverse transcription, HIV cDNA is in complex with virus and host proteins = the preintegration complex (PC)

How can DNA virus inactive Rb protein function?

Amino acid sequence similarities in Rb binding site

What is an emerging virus defined by?

An emerging virus is defined as the causative agent of a new or previously unrecognized virus infection in a population

What may apoptosis be triggered by?

Apoptosis may be triggered by TNFα or by release of cytochrome c

What is the Drug Resistance phenotype

As the curve shifts to the right, a higher concentration of drug would be required to inhibit HIV replication and thus the strain of HIV would be more resistant (= less susceptible)

What is the Baltimore Classification?

Baltimore classification scheme is based on - the central role of the translational machinery - the importance of viral mRNAs in programming viral protein synthesis.

What is poliomyelitis?

Poliomyelitis is caused by an enterovirus - polio virus - spread by oral-fecal contact

What is c-Src and how does v-src differ from c-src?

Cellular c-Src is a cytoplasmic signalling protein that can be phosphorylated at different sites. It responds to extracellular growth factors by binding to an activated growth factor receptor, becoming phosphorylated at certain positions, and subsequently sending a proliferation signal. Cellular c-Src has a C-terminal regulatory region that can also be phosphorylated, but in that case, phosphorylation is an inhibitory event that turns signalling off when the extracellular stimulus is withdrawn. It lacks the regulatory tyrosine near the C-terminus, leading to constant activity and uncontrolled cell growth.

What is the Cellular receptor for CoV?

Cellular receptor is ACE2 ACE-2 distribution - Type 2 alveolar cells - highest - Bronchial epithelia - Tongue > buccal epithelia - Upper Intestinal epithelia - Myocardial cells - Kidney proximal tubule cells - Bladder urothelial cells SARS-CoV-2 binds to ACE-2 receptor ~10-20x more strongly than SARS-C First step in cell entry: binding of spike protein to receptor, ACE2

What are typical sites of virus assembly

Different viruses assemble at various different subcellular locations

How does During latent infection, Epstein Barr Virus (EBV) evades immune detection of EBNA1 and LMP2A?

EBV nuclear antigen (EBNA) 1 protein binds to viral DNA and allows the EBV genome to be maintained in the B cell as a circular DNA episome EBV LMP-2 prevents reactivation of EBV from latently infected cells by blocking tyrosine kinase phosphorylation and allows non-transformed B cells to survive The proteasome is unable to degrade EBNA1, so that EBNA1 epitopes are never loaded into MHC-I. LMP2A can be degraded by the proteasome, but its epitopes are subdominant to cellular peptides and are rarely selected for display

What is the subgenomic RNA transcription model for CoV?

Each coronaviral RNA contains the common 5ʹ "leader" sequence of ∼70 nt fused to the "body" sequence from the downstream part of the genome During negative-strand synthesis, RdRP pauses when it crosses a TRS in the body (TRS-B) and switches ('jumps') the template to the TRS in the leader (TRS-L), which results in discontinuous transcription leading to the leader-body fusion From the fused negative-strand intermediates, positive-strand mRNAs are transcribed

What are social parameters that facilitate transmission of infection to new hosts?

Ecological parameters - Contact with bodily fluids of infected hosts - Sharing a resource with different species - Being host to the same insect vector - Encroachment by one species into the habitat of another

What is the Herpes simplex virus?

Enveloped, dsDNA genome - Herpesviridae Acute gingivostomatitis, herpes labialis, herpetic whitlow, ocular herpes, genital herpes, neonatal herpes, meningitis and encephalitis Herpes simplex encephalitis is responsible for about 10% of all encephalitis cases About 30% of cases result from initial infection with HSV, majority of cases are caused but reactivation of an earlier infection HSV encephalitis can present as neonatal HSVE (mortality rate >25%); or as focal disease following HSV reactivation (mortality 70% in absence of treatment)

How does Flaviviruses provide a simple model for +ssRNA

Enveloped, spherical virions, 10-12kb +ssRNA genomes Flaviviridae, names of the Latin word flavus (yellow) - model species Yellow Fever virus causes jaundice Similar to the Picornaviridae, but Flaviviridae have 5' cap similar to host mRNA. Lack a 3' poly-A tail, instead 3' UTR folds into secondary structures with several stem loops Encodes a single polyprotein that is processed into three structural proteins (C, E1, E2) and seven non-structural proteins

What can glycosylation do?

Glycosylation can mask epitopes on viral spike proteins. The antibody would normally bind to the epitope on the viral spike, but the glycan shield interferes with antibody binding.

What are other subunit vaccines?

Hepatitis B Vaccine - recombinant form of Hep B surface antigen (HBsAg) Influenza virus Vaccine - IV subunit vaccine composed of viral HA & NA - IV cannot replicate - Immune response are humoral

What is Hepatitis caused by?

Hepatitis can be caused by five* hepatitis viruses - HAV, HBV, HCV, HDV and HEV

How do capsids associate with genomes using concerted Assembly?

In concerted assembly, the capsomers and genome come together during genome synthesis assembly and there is no separate empty capsid to be filled The nucleocapsid protein encapsidates new genomes while they are being synthesized. If the virus is enveloped, a later assembly step leads to acquisition of a matrix and envelope surrounding the helical nucleocapsid.

What are the Kinetics of innate and adaptive immune responses to a virus infection?

Innate and adaptive immune responses to viruses are aimed at blocking infection and eliminating infected cells

What are syncytia?

Large, multinucleate cells. - Herpes simplex virus-induced syncytia are shown here.

What are technologies used for vaccine development?

Live Attenuated(weakened or inactivated) - e.g. measles,yellow fever, polio - First introduced 1798(smallpox) Virus-like particle - e.g. Human papillomavirus (HPV) - First introduced 1986 (hepatitis B) Viral vectored - e.g. Ebola - 2019 (Ebola) Nucleic acid - e.g. SARS-CoV-2 - 202 (SARS-CoV-2)

Compare Live viruses and Killed Viruses, for polio in immune response?

Live viruses generate a more complete immune response

How does oncogenesis occur in Oncogene-defieicent retroviruses?

Oncogene-deficient retroviruses, in contrast, do not encode an oncoprotein in their proviral DNA. Instead, oncogenesis is an accidental consequence of exactly where the proviral DNA is inserted in a host chromosome. In a minority of cases, the proviral DNA inserts near a proto-oncogene. The LTR then serves as an enhancer or as a promoter that drives overexpression of the cellular proto-oncogene. This mis-expression then causes overproliferation of the host cell, which sets it on a path toward becoming malignant.

What is the involvement of the viral polymerase (P) in HBV reverse transcription?

P protein becomes associated with 5' epsilon stem-loop, P extends from a modified T nucleotide, copy the bulge (1). P and its associated four nucleotide jumps to the 3' copy of DR1 (2). P extends and synthesizes more (-) DNA (3) while degrading most of the RNA (4). RNA template jumps (5) to pair with complimentary 3' DR2 Polymerase extends from RNA synthesizing (+) DNA (6) The template circularizes (7) which enables DNA to base pair with 3' end of (-) DNA (8) Polymerase extends (+) DNA for about 1000bp before stopping This results in a relaxed, circular genomic DNA All steps are catalysed by P protein which remains bound to 5' end of (-) DNA, throughout

Examples of zoonotic diseases that infect humans causing epidmeics?

SARS-CoV, Horsehoe bat reservior Monkeypox, Monkey

What does dendritic cells stimulate?

Stimulation of a TH cell and a CTL by dendritic cells displaying viral epitopes in both MHC-II and MHC-I. Dendritic cells display the same viral epitope to TH cells in MHC-II and CTLs in MHC-I, allowing the TH cell and dendritic cell to activate the CTL.

How is the B7 receptor is up-regulated by APCs during an innate immune response?

The B7 protein is more abundant on the surface of APCs that have themselves been stimulated by an innate immune response against a virus Abundant B7 protein on the surface of the APC is therefore a sign of danger The use of a co-stimulatory danger signal ensures that the adaptive immune system does not overreact to the billions of harmless microbes that coat most surfaces of the human body. During an immune response, cytokines trigger APCs to up-regulate the B7 transmembrane protein so that it becomes more abundant on the cell surface

How do viruses with RNA genome use host transcription machinery

The host transcription machinery in all cells exclusively uses a double-stranded DNA template to polymerize RNA. Viruses with RNA genomes must have a viral enzyme that can use that RNA as a template, whether to produce antigenomes (complimentary copies of the genome, used as a template to synthesize new genomes), mRNA, or new genomes In the cases of retroviruses (reverse transcribing viruses), a viral enzyme is needed to make a DNA copy of an RNA molecule

What is the Anatomy of respiratory tract?

Upper respiratory tract (URT): - Continually exposed to pathogens - Infections are common ʹ usually mild - Rhinovirus, Parainfluenza virus and Adenovirus Lower respiratory tract (LRT): - sterile environment; - Infections dangerous and more difficult to treat - Influenza viruses ,RSV, (SARS; MERS), and Hantavirus

What is the stable host-virus interaction?

essential for the continued existence of the virus and may influence host survival as well Infected individuals can become ill, recover, develop immunity, or die, yet in the long run, both virus and host populations survive described as an equilibrium - but the interactions are dynamic and fragile, and are rarely reversible Viral populations may become more or less virulent, if such a change enables them to be maintained in the population, while host mechanisms that attenuate the more debilitating effects of the viruses maybe selected.

What is the first stage of virus binding & attachment?

first stage of attachment is reversible binding to host cell surfaces through nonspecific electrostatic interactions between the virion surface and the host cells. Viruses may browse along the surface of host cells before the irreversible binding step of attachment.

Do all viruses have clearly defined capsids?

no

What does mortality mean?

number of deaths divided by the number infected

Define Primary Viremia

progeny virions are released into blood after inital replication at site of entry

How is a confluent carpet of cells made?

the cell population increases in number until all the cells are touching one another without overlapping (A); at this point, contact inhibition (touching other cells on all sides) prevents further population increase

What does host range refer to?

the range of species a virus can infect; in this case, the host range of rabies includes dogs and people.

What is the complex containing RdRP, that produces antigenomes called?

the replicase

What does tissue tropism refer to?

the specific tissues that support virus replication inside an infected host animal. The tissue tropism for rabies is the neurons of the central nervous system

How are Viruses visualised?

viruses are too small to be seen by the human eye, most are too small to be seen by light microscopy light microscopy is an important tool used to visualize the effects of virus infection on host cells

Define Active Viremia

when there is replicating virus in blood

What is Group 5?

( -) RNA cannot be accessed by cellular ribosomes. (+) copies ie. viral mRNA must be made first Viral mRNA is synthesized from ( -) RNA template by vRdRp that is packaged into the virus and is ready to be used upon infection ( -) RNA template is also used to synthesise (+) vRNA intermediate which serves as the template for ( -) vRNA for packaging into new virus particle ( -) RNA viruses with non-segmented genomes synthesise monocistronic mRNAs that code for different viral proteins

What is Group 4?

(+) ssRNA Viral (+) RNA can act as mRNA and directly accessed by cellular ribosomes to translate viral protein Viral RdRp copies (+) strand to ( -) complementary RNA (-) RNA used as template for synthesis(by viral RdRp) of (+) ssRNA for incorporation in new virus particle (+) ssRNA viruses, viral mRNA can be polycistronic

What is Group 6?

(+) ssRNA - RT Retroviruses convert diploid (+) RNA genome to cDNA (RNA dependent DNA polymerase, RdDp) with the viral reverse transcriptase, that is packaged into the virion. - (-) ssDNA acts as template for synthesis of dsDNA intermediate. - This dsDNA is integrated into host cell chromosome with viral integrase. - When cells are activated, viral mRNA is transcribed with cellular DdRp, then translated to viral protein. Viral (-) RNA

What is Barmah Forrest Virus?

(+) ssRNA, enveloped Alphavirus genus, Togaviridae family 2nd most prevalent arbovirus disease in Australia with approximately 2000 cases reported annually The clinical presentation of infection closely mimics that of RRV and involves polyarthritis, arthralgia and myalgia Arthritis is more common and more prominent in RRV disease and rash is more common and florid with BFV infection. However, the diseases cannot be reliably distinguished by their clinical symptoms. Similar to RRV, transmission is maintained in mosquito- mammalian cycle Several mosquito species including Culex annulirostris, Aedes vigilax, Aedes normanensis and Aedes notoscriptus can transmit BFV

What is dengue virus?

(+) ssRNA, enveloped virus Genus Flavivirus, Family Flaviviridae 4 distinct serotypes: DENV-1 - DENV4, which are about 30% divergent RNA genome, exits as quasispecies and as clades or genotypes zoonotic

What are the Pandemic Infleunza's?

1918 - 'Spanish flu' H1N1 1957 - 'Asian flu' H2N2 1968 - 'Hong Kong flu' H3N2

What is Zanamivir and Oseltamivir?

Active vs. influenza A and B Receptor for IV is sialic acid

How can Anti-viral antibodies protect against infection and disease?

Antibodies may inhibit infection by: (a) preventing the antigen from binding its target (b) tagging a pathogen for destruction by macrophages or neutrophils (c) activating the complement cascade

How do Viruses assemble from individual protein molecules

Assembly from folded protein monomers, illustrated with simian virus 40 (SV40) VP1 pentamers. The assembly reaction is the result of specific interactions among the proteins that form structural units. These assembly reactions are driven in a forward direction by the high concentrations of protein subunits synthesized in infected cells, as indicated by the solid arrows.

How is HIV diagnosed?

Australian laboratories use fourth-generation HIV tests (antigen/antibody combination test), which becomes positive 2ʹ6 weeks after exposure

Why do all retroviruses have the ability to cause cancer?

Because all retroviruses replicate through insertion of proviral DNA that includes an LTR, all retroviruses have the ability to cause cancer whether or not they encode an oncogene. Most retroviruses do not infect humans.

Define Secondary Viremia

Delayed appearance of high concentration of infectious virus in blood, following dissemination from initial entry site

What is the first step of influenza transcription?

First step of influenza transcription is cap snatching Influenza A virus produces 10 separate mRNAs, with 5' methylated caps - however, the virus does not encode enzymes to synthesize these 5' caps First step of mRNA synthesis is cap snatching: the cap binding motif in PB2 protein (within vRNP) binds to host mRNA before it leaves the nucleus After PB2 binds to host mRNA, the PA protein (also within vRNP) cleaves the host mRNA between 9 - 15 nucleotides downstream of the cap - cap snatching Cleaved mRNA subsequently serves as a primer for synthesis of mRNA that is complementary to the RNA in the vRNP template RdRp acts in cis to elongate the capped primer using vRNP as template while remaining strongly attached to 5' end of template genomic RNA mRNA is released and the vRNP likely returns to its original configuration

What are the groups of Arboviruses

Flaviviridae - Japanese encephalitis - St. Lois encephalitis - West Nile Togaviridae - Eastern equine encephalitis - Western equine encephalitis Bunyaviridae - La Crosse encephaliti

What caused the spread of the poliovirus in the arly 20th century

For centuries, the host-virus relationship was stable, and infection was endemic in the human population outbreaks of poliomyelitis were seen in Europe, North America, and Australia - not correlated with any substantial change in the viral genome. Emergence of epidemic poliomyelitis can be explained by a change in human lifestyle: unprecedented urbanization and improvement in sanitation. Improved sanitation stopped natural vaccination, most poliovirus infection asymptomatic, inapparent infection in children Paralysis is a more frequent when older individuals are infected.

What has been the focus for the development of anti-HIV medications?

Fusion mediated by HIV has been the focus of intensive research, anti-HIV medications that block fusion The HIV fusion peptide is part of the HIV spike, known as Env. Env has two parts: surface (SU) glycoprotein gp120, and transmembrane (TM) glycoprotein gp41. During penetration, HIV virions fuse with the external surface of the plasma membrane When SU engages a CD4 host receptor molecule, it triggers a conformational change that initiates SU binding to a second host molecule, the co-receptor (such as CCR5 and CXCR4). Binding to the co-receptor then triggers a rearrangement of the gp120-gp41 complex so that a portion of gp41, known as the fusion peptide, inserts into the plasma membrane. Once the virion envelope and the plasma membrane fuse, the HIV nucleocapsid is released into the cytoplasm. Pharmaceuticals that block HIV entry, target this stage by binding to the extracellular helices of gp41 in a way that prevents the conformational changes required for fusion

What is Gancyclovir?

Ganciclovir is an acyclic analog of the nucleoside guanosine Ganciclovir triphosphate is a competitive inhibitor of deoxyguanosine triphosphate incorporation into DNA preferentially inhibits viral DNA polymerases more than cellular DNA polymerases

What is Influenza B?

Generally more mild disease than IVA No reassortment 2 major lineages: Yamagata and Victoria

What is the antiviral state?

Genes induced by interferon are called interferon-stimulated genes (ISGs). They control viral infection in many ways. - e.g. tetherin interferes with viral budding (enveloped viruses - e.g. Mx1 prevents nucleocapsid trafficking - e.g PKR, OAS, and RNase L block translation of mRNA synthesized

How may HDV cause chronic infection?

HDV may cause chronic infection in the presence of HBV

How does HIV escapes immune response?

HIV nef gene product induces expression of FasL on infected T cell surface FasL ligates Fas on HIV-specific CTL and induces death of CTL HIV nef also promotes endocytosis of MHC Class I from cell surface Uncontrolled HIV replication leads to CD4 T cell decline, and AIDS diagnosis

What dissociates Influenza virus RNA from RNP

Influenza virus RNA is dissociated from RNP by acidification of virion interior via viral ion channel M2 protein

What are the killed, Polio Vaccines?

Salk killed vaccine - Formaldehyde-fixed - No reversion - No gut immunity - Cannot wipe out wild-type virus

What describes cancer?

a malignant tumour that spreads and infiltrates tissues, lymph nodes and organs

What is the Ross River Virus?

(+) ssRNA, enveloped Alphavirus genus, Togaviridae family Endemic to Australia (most common mosquito-borne viral disease among humans), Papua New Guinea and other islands in the South Pacific First isolated in 1952 from Ochlerotatus (Aedes) vigilax (salt marsh mosquito) mosquitoes collected near Ross River in Townville; 1971 isolated from blood from an indigenous child with RRV fever Transmission is maintained in mosquito-mammal cycle involving macropods (particularly Western Grey kangaroos) and possibly other marsupials and rodents; horses act as amplifier hosts Spread by different types of mosquitoes with Culex annulirostris, Aedes vigilax and Aedes notoscriptus being most common

What is the diveregance of 2019-nCoV to SARS-CoV

2019-nCoV genomes >99.98% identical 88% identical to 2 bat SARS-like CoV collected Zhoushan 2018 79% identical to SARS-CoV 50% identical to MERS-CoV

What are cancers?

A group of diseases caused by abnormal cell growth - these cells have the potential to spread to other parts of the body metastasize), and in doing so interfere with normal organ function

How do some viruses interfere with Eukaryotic Pol II transcription?

A smaller number of animal viruses are known to shut off host mRNA translation indirectly by interfering with host transcription Host RNA polymerase II (RNA pol-II) is the major enzyme responsible for transcription of mRNA from a DNA template strand One viral strategy to shut off transcription is to proteolytically degrade the TATA-binding protein (TBP), which is necessary for formation of all Pol II transcription-initiation complexes

What is a tumour

A tumour is a swelling caused by abnormal growth of tissue

What is the Influenza A virus antigenic drift and antigenic shift?

A. Antigenic drift occurs when mutations cause influenza A antigens - such as the HA spike protein - to change a small amount over several years B. Antigenic shift occurs when reassortment causes influenza A antigens - such as the combination of HA and NA spike proteins - to change dramatically in a short period of time (such as a single transmission event)

What cellular cytoskeleton elements are required for penetration and uncoating?

A. Organization of microtubules in an idealized cell, showing minus (−) ends at a microtubule organizing center (MTOC) - a centrosome - and plus ends at the periphery. B. Kinesins and dyneins carry cargo along a microtubule. Dyneins move cargo such as viruses toward the (−) ends of the microtubule and therefore toward the nucleus.

How does Viral genetic diversity arise through recombination?

A. Recombination occurs when two viruses co-infect the same cell and an offspring virus contains a combination of genes that originate with both parents instead of just one parent. Horizontal gene transfer is an example of recombination. Homologous recombination is initiated by proteins that recognize regions of identity between two DNA genomes B. Recombination also may occur when a viral polymerase switches templates during synthesis of new nucleic acids; this form of recombination can take place with either DNA or RNA templates C. Viruses with segmented genomes undergo recombination when two different viruses infect the same host cell and segments of different origins assort together into new virus particles.

What is the infecting genome copared to cccDNA, HPV?

A. Viral genome has P covalently attached to 5' end of (-) sense DNA, and to RNA at the 5' end of (+) sense DNA. Has a gapped (single-stranded) region and a trimplex (!) region B. cccDNA is supercoiled dsDNA. Not covalently attached to any proteins does not contain any RNA In both, DNA complementary to direct repeats (DR1, DR2) that were critical for RT in the pregenomic RNA

What is the Acyclovir mechanism of action?

Acyclovir (ACV) is a guanosine analog that is active against herpesviruses ACV is a pro-drug: taken up by herpesvirus-infected cell; viral-encoded thymidine kinase (TK) phosphorylates to ACV monophosphate; cellular enzymes convert to ACV triphosphate HSV TK (not human TK) selectively phosphorylates guanosine analogs such as ACV and ganciclovir (GCV) Inhibits function of viral DNA polymerase - analogs act as DNA chain terminators to prevent further DNA synthesis Active against HSV-I; HSV-2; VZV Applied as topical, oral and intravenous medication - treatment of choice for visceral, disseminated or central nervous system involvement

How do Adenovirus assemble virus particles

Adenovirus genomic DNA molecules contain discrete packaging signals that incorporate viral DNA into assembling virus particles The L1 52-/55-kDa proteins are necessary for the formation of structures that can complete assembly, and decrease in concentration as assembly proceeds. The DNA is then inserted into this structure via the packaging signal located near the end of the genome Core proteins are encapsidated with the viral genome to yield noninfectious young virus particles. Mature particles are produced upon cleavage of the precursor proteins

What are the advantages and disadvantages of Subunit Vaccines?

Advantages: - Prepared from components of virus - proteins. May self-aggregate to produce virus-like particles - Recbominant DNA technology - No viral genomes or infectious virus Disadvantages: - Expensive - Injected - Poor antigenicity In common with inactivated vaccines, viral proteins don't replicate or infect; don't cause inflammation; require adjuvants to induce/mimic inflammatory effects of infection

What is Exogenous antigen presentation by an antigen-presenting cell (APC)?

After a virion is ingested by an APC, it is degraded in a phagolysosome After degradation, the virion's proteins have been broken down so that they are only about 9 to 25 amino acids long Some of these peptides are subsequently loaded into the cleft of MHC-II molecules, and are then transported to the cell surface.

What is Organ invasion?

After dispersal from the primary infection site into blood, subsequent replication requires invasion of new tissues into cells 3 main types of blood vessel/ tissue junction that are routes for virion entry: - Left: continuous endothelium and basement membrane found in CNS, connective tissue, muscle, skin, and lungs: - Centre: Fenestrated epithelium found in choroid plexus, intestinal villi, renal glomerulus, pancreas, and endocrine glands - Right: Sinusoid, lined with macrophages of the reticuloendothelial system, as found in adrenal glands, liver, spleen, and bone marrow

What do Vaccinations aim to induce

Aim to induce long-term immunological memory and protection

What is the Adaptive immune responses to IAV?

Anti-IAV antibodies bind to HA neutralize (1) and opsonize (2) the virions, increasing phagocytosis and destruction of the virions Anti-IAV antibodies bind to NA and inhibit its ability to degrade the sialic acid component of mucus, trapping the viruses in the mucus (3) Anti-IAV antibodies bind to spike proteins on the surface of infected cells and direct the complement to form a MAC on the infected cell, which lyses it (4) Anti-IAV CTLs detect viral antigens presented by MHC-I and trigger infected cells to undergo apoptosis before the virus completes its replication cycle (5)

How may antiviral antibodies ehnance viral virulence

Antibody-dependent enhancement of infection dengue virus, skia virus

What do Antiviral agents target?

Antiviral agents target proteins unique to viruses and essential for their replication cycle Ideally, an antiviral drug does not bind to any normal human proteins but in practice this is rarely achieved good antiviral drug binds to its target virus protein more tightly than it binds to human proteins good candidate targets are viral proteins that play essential role during replication - slows viral replication e.g. fusion proteins, proteases, and polymerases

How can Viruses can block or subvert the cellular autophagy system?

Autophagy can sometimes be part of an antiviral response in which the cell attempts to engulf and subsequently degrade virions or their component parts. In this case, the special term xenophagy is used to denote that it is not the cell's own normal components that are being engulfed and degraded but rather the virus or its component parts. Viral proteins that block many of the individual steps of xenophagy have been described: HIV-1 Nef protein binds to Beclin-1, preventing its activation

What do B-cells do during an anti-viral response

B-cells differentiate to produce high-affinity virus-specific antibodies When the BCR binds to an epitope on the surface of a virus, the B cell internalizes the virus The B cell degrades the virus and ultimately the same epitope that allowed the BCR to bind to the virus in the first place is displayed in MHC-II molecules on the surface of the B cell.

How do viruses subvert receptor-mediated endocytosis for penetration?

Binding of several ligands to their receptors causes them to cluster together, after which the clathrin forms a clathrin-coated vesicle that internalizes the receptors. After internalization, the clathrin proteins are recycled. Viruses usurp this process by mimicking ligand binding, resulting in virus internalization. Receptor-mediated endocytosis occurs after a host receptor molecule binds to its target ligand, which in normal circumstances is a nutrient or growth factor eg. Iron. After a ligand in the extracellular media binds to its receptor, the ligand-receptor complex diffuses in the plane of the membrane until it encounters a small indentation where there is abundant clathrin on the cytoplasmic face of the indentation. The fibrous clathrin proteins then assemble into a cage-like structure that forms an indentation and ultimately pulls the receptor and its ligand into the cell. The clathrin-coated vesicle loses its clathrin and then the vesicle fuses with an early endosome, which is acidified

What is the Geographic distribution of major Bunyaviruses?

Bunyaviruses are a large family of RNA viruses that affect animals and plants. Of the 5 Bunyavirus genera, 4 include human pathogens Orthobunyavirus, Nairovirus, Phlebovirus , and Hantavirus. All but the Hantaviruses are Arboviruses.

What are some persistent viral infections that result in cancer?

Cancer: a collection of many different diseases that are all characterized by the abnormal proliferation of malignant cells that are invasive and ultimately kill the affected animal A small subset of viruses is known to be oncogenic (cancer-causing) in humans Hepatocellular carcinoma is caused by persistent lytic viral infections

What shapes cam capsids take?

Capsids may be spherical (A,E) or helical (F) Spherical capsids are actually icosahedrons Spherical capsids are somewhat rigid helical capsids can be rigid or flexible, depending on the virus.

What is the Hepatitis D virus Infection?

Causes a range of clinical outcomes from asymptomatic infection to fulminant hepatitis Coinfection Both HBV and HDV are acquired simultaneously Severe acute disease/ low risk of chronic infection Superinfection - Chronic HBV carriers are infected with HDV Usually develop chronic HDV infection/ high risk of severe chronic hepatitis - May present as an acute hepatitis Hepatitis D infection can be prevented by hepatitis B immunisation

How do Chaperones contribute to virus assembly?

Chaperones are specialized proteins that facilitate the folding of other proteins by preventing improper, nonspecific associations among sticky patches exposed on nascent and newly synthesized proteins Chaperones are abundant in all cells, and some accumulate to concentrations greater than ribosomes. Genomes of several viruses encode proteins with chaperone activity, some with sequences and functions homologous to those of cellular proteins

What is the Hepatitis D virus?

Circular, ssRNA(-) genome of 1,68 kb Unique virus dependent on HBV - enveloped (HBsAg) Considered a satellite virus of HBV but does not share sequence similarity; can replicate independently of HBV

How do Some viruses and hosts coevolve?

Coevolution of certain lentiviruses and African monkeys provides an example in which the two interacting populations cospeciate Lentiviruses are complex retroviruses that include two species of human immunodeficiency virus (HIV) and more than 40 simian immunodeficiency virus (SIV) species, which each infect just one primate host species Host switching, in which a virus jumps from one species to another, is very rare, even though it accounts for the origin of HIV Coevolution of SIV and their hosts has occurred, and can be observed at the molecular level by examining viral proteins and the host restriction factors they interact with. Host restriction factors are innate animal defense proteins that limit or prevent infection by particular groups of viruses

How does virus entry occur via alimentary tract?

Common route of infection and dispersal Extremely hostile environment for virions - stomach is acidic, intestine is alkaline, many digestive enzymes and bile detergents, intestine is lined by mucous, lumenal surface includes antibodies and phagocytes Some viruses eg. Poliovirus can replicate in low pH environment. Changes in capsid that occur under acid conditions are fully reversible; low pH induces irreversible disassembly of the rhinovirus capsid

How is Human innate immunity is triggered by pattern recognition?

Common structural features unique to microbes compared with human beings are called pathogen-associated molecular patterns, or PAMPs These PAMPS bind to pattern recognition receptor proteins, PRRs, triggering an innate immune response.

What is the infection of the Murray Valley Encephalitis Virus?

Commonly subclinical, or fever and headache - approximately 1:150-1:1000 infections develop into clinical encephalitis - altered mental status, convulsions and coma 4 week incubation Case fatality rate of encephalitic MVEV is between 15-30%, with long-term neurological sequelae occurring in 30-50% of survivors and only around 40% recovering completely

What is a comparison of HIV RNA genome and proviral DNA?

Comparison of HIV RNA genome and proviral DNA: 5' end of the genome differs in sequence from the 4' LTR. THe 3' end of the genome is poly-adenylated, while in the provirus there is another copy of the LTR. The provirus is flanked by host DNA

What are Nucleoside Reverse Transcriptase Inhibitors (NRTIs)?

Competitive inhibitors of viral polymerases, including HIV reverse transcriptase - Normal DNA chain extension requires covalent bonding of the 3' carbon on the deoxyribose or ribose sugar and one of the oxygen groups associated with the phosphates on the incoming nucleotide triphosphate - The reaction requires a hydroxyl (OH) group on the 3' carbon - Drugs that mimic nucleotide triphosphates in their active form, often lack the OH group required to add the next nucleotide to the growing chain - NRTIs compete with natural dNTP/NTP substrates for incorporation into the nascent viral nucleic acid, and so act as chain terminators - AZT was the first approved HIV-1 antiretroviral drug, it is a chain terminator Because AZT has an azido (NH3) group on the ribose instead of a hydrogen, the next base cannot be added to the DNA chain - DNA synthesis stops

What is the role of the complement system in viral control?

Complement is a collection of soluble proteins found in the blood and lymphatic system. Activation requires a cascade of several molecular events that must occur in a specific order. Once activated, infection is counteracted in 3 ways: 1. MAC 2. Opsonisation of extracellular virions 3. Chemoattraction

What is Carcinogenesis?

Complex multistage process by which cancer develops

How does the modulation of the adaptive immune response perpetuate a persistent infection?

Cytotoxic T lymphocyte (CTL) response is one of the most powerful adaptive host defences against viral infection Host CD8+ T cells must detect viral antigen present on the surface of infected cells in order to kill them Recognition requires presentation of viral peptide antigens by MHC Class I proteins on cell surface Persistent viruses may escape CTL killing by mutation within gene regions which encode the CTL epitope

What is the SARS-CoV-2 Genome Organization, Subgenomic mRNAs, and the Virion Structure?

Each viral transcript has a 5ʹ-cap structure and a 3ʹ poly(A) tail). Upon cell entry, the genomic RNA is translated to produce nonstructural proteins (nsps) from two open reading frames (ORFs), ORF1a and ORF1b. Proteolytic cleavage of the polyproteins is mediated by viral proteases Viral RdRp (nsp12) transcribes (-)sense RNA that serves as template for synthesis of (+) sense genomic RNA (gRNA), and subgenomic RNAs (sgRNA) gRNA is packaged with assembling virion sgRNA encode spike (S), envelope (E), membrane (M), nucleocapsid (N) and several accessory proteins

What is the resistance of Nucleoside Reverse Transcriptase Inhibitors(NRTI)?

Emergence of discriminatory mutations Discriminatory mutations allow the viral reverse transcriptase to preferentially select naturally occurring deoxynucleotides present in the cell creates a relative decrease in incorporation of NRTI-triphosphate into the elongating HIV DNA strand

What is a review of transcription?

Eukaryotic transcription occurs in the nucleus and is catalyzed by RNA polymerase RNA polymerase II (Pol II) catalyzes mRNA synthesis, from a dsDNA template Mature mRNA in the nucleus is exported to the cytoplasm through the nuclear pores as a messenger ribonucleoprotein (mRNP) complex

What is Hepatitis C virus?

HCV particles are spherical and heterogenous in size, ranging 40-80 nm Flaviviridae family, Genus Hepacivirus In the bloodstream, HCV can circulate as a hybrid lipoviral particle that consists of lipoproteins tightly associated with the HCV particle. - The formation of the lipoviral particle facilitates HCV entry into hepatocytes and it protects HCV from antibody neutralisation.

Why is the HIV-1 diversity high?

High mutation rates (low fidelity of RT/ host cell factors); Retroviral recombination (via template switching); High viral turnover, host immune system selection, etc.

How does the human herpesvirus establish latent infection?

Human herpesvirus establishes latent infection in neurons Latent herpesvirus infections - HSV-1 and HSV-2 - begin with lytic infection of an epithelium Virus replicates in the epithelium and latency is initiated when some of the offspring virions infect the sensory neurons that innervate the epithelium Virions that enter the terminally differentiated neurons traffic along the cytoskeleton to the cell nucleus, in the spinal column Herpesvirus genome circularizes and persists as an episome in the nuclei of latently infected cells Multiple copies of episomal viral DNA remain in nucleus

What is Influenza C?

Infection is associated with minor symptoms

How does Human metapneumovirus modulate host immune response?

Inhibition of T cell priming is partially dependent on the secretion of soluble factors by HMPV-infected DCs, which impair the upregulation of the TCR-driven activation marker CD69 and the proliferation of stimulated T cells Downstream effect on activation of B cells

What are viral replication complexes(VRCs)?

Many viruses that replicate in the cytoplasm compartmentalise genome replication and transcription of proteins to virus replication complexes (VRCs) Escape recognition from host defences, recognition by toll-like receptors VRCs assembled by non-structural viral proteins, viral genomes, host lipids and host proteins Within the VRC the + strand genome is used as a template to synthesize full-length anti-genomes (- sense), which remain hydrogen bonded to the + strand dsRNA intermediate (the replicative form) can be recognised by the innate immune system

What is Muller's ratchet?

Muller's ratchet: small, asexual populations decline in fitness over time if mutation rates are high

What do RNA viruses exist as?

RNA viruses may exist as quasispecies

What is the Coronavirus Structure?

SARS-CoV-2 has surface viral proteins, namely, spike glycoprotein (S), which mediates interaction with cell surface receptor ACE2. The viral membrane glycoprotein (M) and envelope (E) of SARS-CoV-2 are embedded in host membrane-derived lipid bilayer encapsulating the helical nucleocapsid comprising viral RNA

What are the Live, Polio Vaccines?

Sabin attenuated vaccine - Grows in epithelial cells - Does not grow in nerves - No paralysis - Local gut immunity (IgA) - ~10 cases vaccine associated polio per year - 1 in 4mill vaccine infection

What are host determinants for transmission at population level?

Social contact patterns - mode of transmission age-related mixing patterns - age-specific risk of transmission

What are the majority of human encounters with viruses?

The vast majority of human encounters with viruses are uneventful because host cells are not susceptible or the body's defenses are so strong that potential invaders cannot initiate an infection

What is the R0 of SARS-CoV-2?

Typically cited as 2-3 but may be as high as 4.9; varies by population density and exposure patterns Probably about twice as transmissible as influenza

How do Some viruses evade the CTL response?

Viral evasion strategies include: An abundant viral protein to be resistant to degradation by the proteasome (1). to prevent transport of peptides from the proteasome into the ER through TAP (2). to target vesicles containing MHC-I-epitope complexes to the lysosome so that the complexes get degraded and never reach the plasma membrane (3). to prevent the MHC-I-epitope complexes from leaving the Golgi apparatus so that they never reach the plasma membrane (4).

What is the Viral Evasion of NK cells?

Viruses can evade this NK cell killing in a number of ways, e.g. - Encoding viral MHC-I homologs which mimic host MHC-1 and can engage the NK inhibitory receptor - Produce anti-apoptotic proteins to prevent cell death

How must viruses transcribe mRNA

Viruses must transcribe mRNA that either has the genuine features of normal cellular mRNA specific for its particular host cell type or must mimic or functionally replace these features so that the viral mRNA can be translated.

How do developments in methods for virus discovery drive the identification of viruses that infect humans?

a. Discovery by species of virus b. Discovery by virus family c. Technological advances through the 20th century to the present

What is an inclusion body?

abnormal internal structures visible when the host cells are stained. Form in the cytoplasm or nucelus depending on the virus inclusions turn out to be the sites of viral gene expression, genome replication, assembly, or some combination of these. e.g. Rabies virus inclusion bodies are visible in the cytoplasm; 2 are pointed out by arrows.

What are the capsomere that surround nucleic acid called?

capsid

What must assembly take into account?

cellular protein localization Progeny genomes, structural proteins, and enzymes of virus particles must be concentrated at the intracellular site at which assembly takes place When viruses with DNA genomes are assembled in the nucleus, cytoplasmic proteins must be actively imported The particles of many viruses that reproduce in animal cells include a lipid envelope derived from a host cell membrane host cell, and therefore assembly takes place at a cell membrane All proteins destined for insertion into the plasma membrane enter the ER as they are translated. The ER lumen is the site of many essential protein modification and folding reactions Viral glycoproteins may be proteolytically processed in the Golgi network, a reaction essential for the formation of infectious particles The envelopes of a variety of viruses are acquired from internal membranes of the infected cell, rather than from the plasma membrane

How is the number of infectious virus particles needed to infect cells determined for plaque-forming viruses?

determined by plaque assays

What are Non-nucleoside RT inhibitors

dont bind in the active site of HIV RT, they inactivate by binding elsewhere problem: onset of resistance is very rapid still useful in combination with other drugs Nevirapine is NNRTI used to reduce transmission of HIV-1 from mother to child during childbirth, given as a single dose close to delivery

How is the number of infectious virus particles needed to infect cells determined for non-plaque-forming viruses?

endpoint dilution assay

What is the general process by which latent infections act?

human herpesviruses such as varicella-zoster virus cause latent infections of certain host cells In general, these viruses replicate lytically when they first enter the human body and subsequently infect quiescent or terminally differentiated host cells where the viruses establish latency Reactivation occurs upon weakening of the immune system or exposure to stress as in herpes simplex virus infections. A typical example is the extremely painful condition known as shingles that results from reactivation of VZV, which causes chicken pox when a person is infected for the first tim

What is the origins of vaccination?

inoculation with cowpox protects against smallpox - a closely related Orthopoxvirus - Edward Jenner 1796 James Phipps is inoculated with vaccinia virus (cowpox) taken from milkmaid Sarah Nemes