Virology Exam 2

Measles

(one of the most contagious diseases) Family: Paramyxoviridae How it goes into the body and moves around Airborne- and flung into air when someone sneezes or coughs Can live up to 2 hours in air and on surface if 1 person gets it 90% of nearby non-immune people will get it Once inside The virus affects the epithelial cells of the Trachea and Bronchi It uses its Hemagglutinin protein (H proteins) on the cell surface to bind to the surface of the host cells The cell receptor is CD46~ This is on all nucleated human cells And SLAM- B/T cells and Antigen Presenting cells Nectin-4 a cellular adhesion molecule It uses its Fusion protein (F protein) to fuse with the cell Releases its RNA Genome SS (-) RNA virus Needs to be transcribed with RNA polymerase to a Positive sense mRNA strand Its ready to be translated into Viral proteins Its wrapped in the cells lipid envelope Sent out of cell as newly made virus Once it leaves the cell it attack local tissues - Dendritic cells and Alveolar macrophages Carries it to the lungs and local lymph nodes Goes through blood and then more lung tissue, intestines and brains 10-14 days from when virus enters body to the start of symptoms (incubation tissue) Timeline Onces symptoms start - prodromal period 3 days Starts with high fever and cough, conjuntivitis (redding of eye) and Coryza (swelling of mucus glands- stuffy nose) Later comes the enanthem (rash on the mucous membrane)- koplik spots- white spots inside the cheeks opposite of molars Exanthem Phase- red blotchy maculopapular rash that spread cephalocaudal progression(spreads from head to extremities)- 4 days Recovery Phase- 10-14 days- final symptom is a final cough MOST contagIous during last day of incubation up to end of exanthem Lifelong immunity of measles Affects the lungs (pneumonia), Intestines (diarrhea) and Brain (Encephalitis) - all can lead to death Suppresses immune system for up to 6 weeks Can lead to bacterial superinfections: Otitis Media and Bacterial Pneumonia Most complications in infants with the highest mortality rates Complications for children under 2 - Subacute Sclerosing PanEncephalitis (can happen 7 to 10 years later) Cause- maybe persistent measles infection possibly cause by abnormal immune response or mutated strain of measles virus Leads to chronic inflammation of Entire Brain Symptoms include: Initial subtle mood changes Eventually severe to cause seizures, coma and death People with Immunocompromised and get measles Won't show certain symptoms like the koplik spots(Enanthem) or rash (Exanthem) Higher rates of pneumonia and encephalitis which leads to a higher mortality rate Diagnosis Serology- look for measles antibodies in Blood Serum Vaccine- live attenuated Virus Given 12 - 15 months of age & 4-6 yrs 95% vaccine efficacy rate Anti Measles antibody (immunoglobulin) is passed on from mother to fetus across the placenta and will last 9 months. Treatment No specific antiviral treatment Medication Treat superinfections, maintain hydrated and pain relief Epidemiology 2000: thought to have eradicated measles, US nonexistent 2019: measles cases on the rise, probs because of anti-vaccination movement in US, Dominican Republic of Congo had outbreak

Norovirus:

- Family: Caliciviridae family - Small, non-enveloped viruses (very small genomes) Unique qualities: - VPg on 5 prime end and a 3 prime polyadenylated tail (poly-A-tail) that is involved in replication. - Also uses subgenomic mRNA to make structural proteins VP1 and VP2. - Major polyproteins encoded by ORF1 are RDRP and Protease. ORF2 encodes VP1 (for formation of capsid structure) and VP2 ( a minor structural protein). - Do NOT know cellular receptors for Norovirus however it attaches to HBGA's on RBCs affecting how certain blood types may become resistant to certain strains. Replication for Norovirus: 1. Noroviruses come in and bind to its cellular receptor on the host surface. 2. We think it enters through receptor-mediated endocytosis. 3. Once inside the cell, noroviruses like other positive ssRNA viruses uncoats, and it's RNA is in the cytoplasm and is available immediately to be translated by the host ribosome. 4. Ribosomes bind to the VPg (has a VPg like poliovirus) and begin the process of translation. 5. Once viral polyproteins are made, they get cleaved into individual proteins by protease. 6. Once these individual proteins and RdRp are made, copying of the viral genome can begin. 7. RdRp binds to the 3 prime end at the poly-A-tail and begins de novo (new) copying of the negative ssRNA genome. - It binds to a newly made negative strand and makes another positivenew strand. 8. This néw positive strand can be used as a template or capped by VPg and used to make more viral proteins. 9. Many copies of proteins are being made and translated and when there's enough proteins, they self assemble around newly made and capped viral RNA to form new viral particles. 10. New viral particles lyase the cell and go on to infect other cells within the body. Epidemiology for Norovirus: - Leading cause of GI illness worldwide. - Globally, 685 million infections with 50,000 deaths. - In the US, 20+ million infections and 600-800 deaths Equal Opportunity Pathogen: - Infects all ages, no one is more or less susceptible. - Death rarely occurs in healthy individuals, and 20% of people genetically resistant. - Noroviruses use HBGA's- histo blood group antigens- to cause infection. Each specific strain binds to a specific HBGA. - These strains are evolving rapidly and new ones are always forming, so no one is completely immune Symptom: begin within 24 hours of ingestion, the major symptom is diarrhea, accompanied by vomiting, nausea, and headache. -self limiting infections resolve within 18-48 hours Treatment/Prevention: oral rehydration, no drugs or licensed vaccines available. *Perfect Pathogen* = there is no lasting immunity Infectious Phases: - Acute/Symptomatic= first 24-72 hours, lots of virus in the feces. - Persistent Infection- can last 3 wks- 2months, the individual is asymptomatic, but shed less in stool. Transmission: Fecal to oral route, which makes the virus highly infectious and very easily spread. (infectious dose is 10-1000 viral particles) -environmentally stable virus, and spreads well in close community settings, with the highest percentage being in restaurants. Outbreaks: tend to occur in cyclical fashion due to viral evolution -the peaks are due to evergrowing new strains of the virus, and the quiescent periods are related to short term herd immunity (quiet periods of virus) Unique cellular tropism: Acute Infection attacks IMMUNE cells. T cells>dendritic cells>macrophages. Persistent Infection attacks EPITHELIAL cells Specialized cells called Tuft cells are primarily infected and these cells share qualities with neuronal cells. - How this virus shifts from attacking immune to epithelial is unknown!!

That replication occurs associated with membranous vesicles.

-Theoretically, this helps the RNA and enzymes together so that everything is in one place for replication. -From the textbook: Efficient packaging of progeny RNA. Provides lipid components & support. Might protect viral nucleic acids from nucleases.

T/F: The rotavirus genome gets released into the cytoplasm prior to the generation of mRNA.

False

Influenza has a segmented genome

Most segments encode only one protein but some can produce multiple proteins via frameshift or alternative splicing

Mechanisms of entry/uncoating for ss (+) RNA viruses

Picornaviruses and Flaviviruses- bind to a cellular receptor and enter through RME. Uncoating occurs in the cytoplasm where the genome is immediately translated. Dengue - RME then fusion with the endosomal membrane, etc

Parvoviruses

Single stranded DNA virus Parvoviridae family Parvovirus Human B19 virus (erythrovirus) Human Adenovirus-Associated Virus (AAV) Small size and small genome Does not encode very many viral proteins, thus rely very heavily on host cell to produce viral proteins and replicate the virus Infection in humans = fifths disease Human Adenovirus-Associated Virus (AAV) Dependo-virus Can't replicate in a host cell without the help of another virus In AAV, the virus that provides the help is adenovirus Genome ssDNA genomes must be "repaired" before transcription can occur These viruses cannot copy their genome until at least one viral protein is made mRNA needs to be made before anything else can happen mRNA can only be made from dsDNA so the ssDNA virus has to convert its genome to be double stranded to then make mRNA Has terminal repeats at either end that cause genome to form hairpin-like structures at both 5' and 3' ends Two open reading frames (ORFs) One encodes for genes involved in replication (rep ORF) The other one encodes genes in capsid production Origin of replication Point where polymerases will bind and allow for copying of DNA template Replication (*AAV viruses - similar for other parvoviruses) First binds to cell surface receptors (lots of cell surface receptors they can bind to) Common one: heparan sulfate Once inside cell, AAV migrates to nucleus Due to small size, can enter through nuclear pore, so entire virus particle is able to enter into the nucleus Once here, ssDNA needs to be made into dsDNA so mRNA can be produced First step in replication process: transforming ssDNA genome into dsDNA Conversion of dsDNA is done by host DNA polymerases mRNA is made and transported into the cytoplasm where it can be translated by ribosomes First viral protein made is Rep 78/68 protein This protein will migrate back into nucleus and play a role in copying of DNA genome for insertion of genome into new viral particles When genome is copied, both positive and negative strands of DNA are made (**very unique about single-stranded DNA) Both negative and positive strand can be packaged into new viral particle (genome is not polarity dependent) Rep 78/68 protein also helps activate transcription of other AAV genes, which results in production of more Rep 78/68 protein and production of structural proteins Proteins are translated in the cytoplasm and then migrate back into the nucleus where new viral particles are assembled Once particles are formed, virus exits the cell Replication in Greater Detail (Strand Displacement) ssDNA genomes are made through strand displacement Genome structure with terminal repeat hairpin ends Cellular polymerase comes in and repairs viral genome Result of transcription = 78/68 protein molecule Rep molecule comes in and nicks the viral genome at other end of terminal repeat Host DNA polymerases come in and make copy of hairpin sequence, so now you have two hybrid strands of DNA One part of strand = template DNA that came in with virus Other part = newly made piece of DNA Two hairpins form, and an ORI can be bound by host DNA polymerases Polymerase comes in and begins to make a copy of the genome As it copies, it displaces one of the original strands At end, left with DNA genome with partial of old original viral DNA as well as newly made synthesized DNA Now also have one double stranded DNA genome which can serve as a template for making mRNA or it can be nicked by Rep 78/68 to make more genomes Continuous cycle that keeps happening over and over Hosts Commonly causes disease in animals Can cause deadly disease in both dogs and cats In DOGS: "Canine parvovirus" Presents with vomiting diarrhea, and fever Can rapidly progress into something fatal as animal becomes very dehydrated and can lose blood through injury to intestinal lining In CATS: Called "feline pan leukemia virus" Highly infectious and very fatal Causes dehydration as a result of ulceration of the intestinal lining Results in bloody diarrhea Like in dogs, dehydration commonly causes death In human infections, parvovirus is pretty benign Several types of parvoviruses can cause disease in humans B19 Virus - causes fifths disease Begins with fever and headache Once fever breaks, whole body breaks out in a bright red rash Very common in children Infection almost always resolves without any further incident

Some symptoms of influenza infection are caused by inflammation which results from infection, while other symptoms are the result of the immune response against the virus.

Spanish flu cytokine storm: systemic inflammatory response, reason for higher mortality among younger people with stronger immune systems

For ss positive RNA viruses, which protein is responsible for copying the genome?

The RNA-dependent RNA polymerase AKA RdRp

Retroviruses

Unique features: - Has a spliced mRNA. - Has two copies the RNA. - Coated with nucleocapsid proteins. - Has STOP codons. Enveloped Virus - Lipid bilayer surrounding the viral capsid. - Matrix proteins underneath the envelope. Capsid Shape: icosahedral Glycoproteins: Protrude out of the envelope, Surface proteins (SU), and Transmembrane proteins (TM ). Viral proteins packaged: Protease, Integrase , and Reverse Transcriptase (packages 50-100 copies per viral particle). Genome structure and method of transcription/translation of retroviruses: - Two structural features of the retrovirus viral genome: 1. Long terminal repeats (LTR) located in the 5 prime and 3 prime ends involved in the integration process. 2. In between the long terminal repeats you have the viral coding region which contains all of the viral genes and proteins that are eventually transcribed and translated. - Integrated DNA (provirus) is going to be transcribed by the host cell DNA polymerase to make mRNA. -The mRNA that is made is a full length copy of mRNA, and this is the RNA that's transcribed and translated into proteins and it's also going to be found inside the virus particles. - Once the mRNA is made, the process of expressing these genes into viral proteins is different from other (+) ssRNA viruses. -Those viruses make one long polyprotein from a single RNA genome and that polyprotein gets cleaved by the viral enzymes to produce proteins that the virus needs to replicate. Production of polyproteins occurs in several stages: - First stage: you have the translation of the gag proteins which is the first poly protein that is made. This gets cleaved by viral proteases into various structural proteins. - After the gag protein, there's a stop codon that causes the ribosome to fall off the RNA. - In order for the other genes on the mRNA to be expressed, this stop codon has to be suppressed or inhibited. When it gets suppressed, the ribosome can continue to read and translate the proteins farther down the RNA and eventually make all the proteins. - This results in the formation of a longer polyprotein called the gag pol precursor. This has the proteins for the reverse transcriptase and are cleaved by the viral protease. *the stop codon doesn't get suppressed all the time, it only gets suppressed 10% of the time. If the stop codon doesn't get suppressed, then the new viral enzymes (including Reverse Transcriptase) could never be made. - In addition to the full length mRNA, there is a separate spliced messenger RNA that is made by the cell. It is this spliced mRNA that is translated to generate the envelope proteins. - There's another stop codon after the pol sequence and there's no suppression of the stop codon. So the only way that the envelope glycoproteins can be made is through the splicing mechanism. - Splicing is a very common mechanism for generating mRNA in our cells. Our cells use it to express host genes. - The sequence between the 3' and the 5' end of the splicing mechanism is what gets spiced out and allows for the translation of the enveloped proteins. Retrovirus integration into host chromosome: 1. This process begins after the viral genome has been converted into DNA. 2. The integration reaction is catalyzed by the viral enzyme integrase. 3. The are two features that happens when a retroviral DNA sequence gets inserted into the host gene: a. Some of the bases at the end of the LTRs lost from viral DNA. b. Before integration (pre-integration) you have four bases at the ends in the LTRs, after integration you have 2 bases within the viral genome integrated into the host. c. Duplication of the host DNA at the insertion site. This is seen in the strand that has been integrated already with the host chromosome and the viral genome. The way that integrase degrades the DNA is that it exposes free hydroxyl groups at the ends of DNA and then the enzyme can use the free hydroxyls to catalyze the cleavage of the host DNA. Once this cleavage occurs, the viral DNA can bind to the cleaved host DNA. Host repair enzymes will come in and fill the areas where the viral DNA has joined up with the host DNA. - Integration can happen anywhere on the host chromosome ○ Integration of viral dna into the host dna can happen anywhere its not site directed or in a specific place but once it happens, its permanent.

Cell types infected

- Mainly infects T cells: but can infect other cell types with CD4 receptor such as macrophages and dendritic cells.

Which of the following are important features of single stranded DNA replication? Check all that apply.

- The use of host cellular enzymes in DNA replication and the function of the Rep 78/68 protein.

Types of parvoviruses that cause disease in humans and animals

-Human B19 virus, Erythrovirus. -Human Adenovirus- Associated virus AAV = dependovirus. -Canine parvovirus: vomiting, diarrhea and fever in dogs. -Feline pan leukemia: dehydration as a result of the intestinal lining.

Why are parvovirus infections in animals commonly lethal?

Because infections result in dehydration which can lead to death.

Why must double stranded RNA viruses package an RNA-dependent RNA polymerase (RdRp) inside their viral capsid?

Because the positive of RNA in their genome cannot function as mRNA.

T/F: single stranded DNA viruses only package a positive strand of DNA into new viral particles.

False

T/F: Host enzymes cleave the viral polyprotein into individual proteins.

False Explanation: Not host enzymes, the viral enzymes cleave the viral polyprotein

Differences between alphavirus replication compared to other ss (+) RNA viruses.

For most ss positive RNA viruses when the 1st viral proteins are made (RdRp), these non structural proteins go on and replicate the genome on membranous vesicles. HOWEVER, in alphaviruses, this initial translation will not translate the entire viral genome, they need to go through a negative sense intermediate in order to access the coding region of mRNA that the virus needs to use to make structural proteins.This small piece of mRNA is called subgenomic mRNA. Once this is made, viral structural proteins can be translated and the rest of the cycle can take place.

Inverted terminal repeats form which important structures of linear single stranded DNA molecules?

Hairpin structures

Rabies: rhabdovirus family

Infection: animal bites - virus goes inside your muscles and replicates in there- gets into sensory and motor nerves- travels by retrograde external transport to the spinal cord where it jumps across synapses and into the next neurons and finally travels up to the brain Affects neurons- will have negri bodies (viral proteins in the cell that will clump together) After it replicates in the brain it can now spread back outward to the eyes and salivary glands Everybody is vulnerable- Very rare but extremely deadly Symptoms- 100% fatal Incubation period- 1 week to 1 year Treated with vaccine after infection (before symptoms show)- very unique What it looks like: Prodromal Phase Flu like symptoms Nausea/ vomiting Encephalitis Respiratory and vascular collapse Fever, agitation Hydrophobia Pharyngeal spasms, flaccid paralysis Seizures and coma

What enzyme comes packaged in the Influenza viral capsid, attached to the negative RNA segments?

RNA polymerase

The characteristics and epidemiology of infection and disease for rotavirus

- #1 cause of severe childhood diarrhea. - Affects GI tract first with an enterotoxin. - Incubation period is 2 days and the symptoms are non bloody diarrhea, vomiting, fever that can last for a week. - Deadly b/c diarrhea = dehydration = death

Immune amnesia caused by measles

- After someone recovers from measles, they are more susceptible to other infections. - Person infected with pathogen, immune system develops specific subsets of B cells and T cells that are specific and long-lasting AKA memory cells. - Able to more quickly react, memory immune response results in no symptoms or shorter/ less severe. - Memory immunity protects against future infection. - Vaccination elicits memory immunity and this is how vaccines are effective in preventing infection. Elicit response in absence of infection or disease. - Infections with measles can erase a person's memory immune response. - SLAM receptor found on many B and T cells. - Virus comes in contact with memory cells and infects them, killed by viral replication or die because of host immune response. - Loss of memory immunity for whatever pathogen they respond to: - Memory cells that are destroyed are replaced by memory cells for measles virus. - Very strong immunity against measles. - Loses immunity against other pathogens. - Body is capable of regenerating memory immune cells when reexposed to a pathogen. - Healthy individuals take 2 years to recover protective immunity and 5 for children. - Immune amnesia appears to be linked to severity of infection. - Doesn't occur in response to vaccination, attenuated virus doesn't infect memory cells but does provide immunity.

Integration of retroviral DNA into the host chromosome results in characteristic changes to both the viral DNA and the host chromosome.

- Bases lost from LTRs. - Duplicate host DNA at insertion site.

Similarities between ss positive RNA genomes and mRNA

- Both have 5 prime and 3 prime untranslated regions (UTRs) - Have 3 prime polyadenylated tail (poly-A-tail) - Have a protein link at the 5 prime end (5' cap). - Polio and noroviruses are different, they have a viral protein: VPg ( serve as primer for viral replication)

Know the similarities and differences between replication of VSV and influenza.

- Both: Negative RNA move into the cell and need to be made into strand positive RNA, and ultimately need to make negative strand genome. - Difference: VSV's mRNA that they synthesize cannot be turned directly into neagtive RNA genome b/c they are segmented due to start and stop codons on the original negative strand. - Difference: Influenza's mRNA cannot be turned directly into negative RNA genome b/c each segment has an extra sequence from the host cell on its 5 prime end, and is truncated by 20 nucleotides on the 3prime end. - Both: Mechanism to solve these problems is similar, using N and Np proteins respectively, they prevent the segmentation in VSV and prevent the truncation in Influenza.

Which characteristic of Measles infection is linked to development of immune amnesia?

- Destruction of memory immune cell: Measles virus infects and depletes pre-existing memory lymphocytes, causing immune amnesia. Studies detect infected memory CD4+ and CD8+ T cells and naive and memory B cells. There are reduced frequencies of circulating memory B cells and increased frequencies of regulatory T cells and transitional B cells after measles. Measles Virus infects cells after binding to cellular receptors CD150 or nectin-4. In a study of the virus, it initially targets myeloid cells in the respiratory tract.

The symptoms, characteristics and phases of HIV infection

- During acute infection the R5 strain of HIV, which binds to the CCR5 co-receptor, will get into macrophages, dendritic cells, and T-cells. There are usually flu-like symptoms during the acute infection. - Counterattack: where the body is able to control HIV replication. - The chronic phase can last 2-10 years. In this phase virus increases and T-cells decrease. - Symptoms: swollen lymph nodes, hairy leukoplakia white patch on tongue, caused by Epstein Barr, oral candidiasis.

Specific cell types infected by the viruses above.

- Ebola: Dendritic cells, macrophages and monocytes and by doing so, it disrupts the immune response and normal cellular processes. - Rabies: Muscle cells, nerve cells, (negri bodies) CNS - Measles:Dendritic cells and macrophages

Dengue, single stranded positive RNA virus

- Enveloped virus - Unique features: Forms spike like structures as a result of low pH and then fuses with the endosomal membrane. The viral RNA forms a circle prior to joining with the replication complex Dengue Attachment, Entry, and Replication: 1. Dengue enters the cells and releases its genome into the cytoplasm on lumen side of endoplasmic reticulum. 2. Proteins form replication complex on the surface 3. RNA forms a circle and attaches to the replication complex to begin synthesis. 4. Negative sense strand is made, and the pair of RNA strands form a double helix. Afterwards, the negative sense is now a template to create a positive sense strand. 5. The envelope proteins aggregate on the lumen side of ER, and capsid proteins cluster on cytoplasmic side. 6. Dengue virus gets its envelope from the ER and uses natural secretory pathway of the host cell to leave the cell Anibody Dependent Enhancement (ADE)in Dengue: - Antibodies can make subsequent Dengue infections WORSE. - If you are infected w/ Dengue a second time with a different strain than before, antibodies bind to the strain but CANNOT neutralize it, which allows the new strain to bind to a second receptor Fc (antibody) receptors on the cell surface. - Results in increased infection and suppressed viral immunity b/c the virus can now bind to cognate AND Fc receptors (basically tricking the cell and receptors). - The SECOND infection with Dengue is worse than the FIRST

Influenza is one of the most widespread and deadly viral infections that occurs each year.

- Genetic/antigenic drift generates slightly new forms from mistakes in replication. - Genetic/antigenic shift generates very different, new forms from horizontal recombination. Co-infection leads to RNA segments from each of 2 different strains coming together.

Mechanism of replication for ssDNA viral genome

- Genome must be repaired before transcription using host enzymes. - There are two terminal repeats (TRs) at the 5 prime and 3 prime ends in form of hairpin. - The host DNA polymerase repairs the viral genome then binds the terminal repeat and flattens the hairpin and copies it. - Rep78/68 nicks at the other terminal repeat. - Hairpins reform and are bound by host polymerases. - Upper strand is displaced to make ssDNA.

Importance and impact of HIV error prone replication

- HIV Reverse Transcriptase is notorious for making errors when it replicates, and that during infection it can mutate to create slightly different strains of viruses. - These viruses are still considered HIV, but they behave slightly different from each other and target different cells in the host. That host cell preference is called viral tropism. - There are 2 strands of ss positive RNA in the virus because it increases the chance that one of them will still be functional if the RT makes an error.

How virus enters via membrane fusion and the proteins used in attachment and entry

- HIV uses the CD4 receptor on the host cell mainly T Helper cells to bind the envelope protein and cause a conformational change. - It also uses a coreceptor known as chemokine coreceptor CCR5 to grab hold of the envelope protein by triggering the extension of the fusion protein. - Binding of the CD4 receptor causes the conformational change that allows for the interaction of CCR5. - The stalk of the envelope protein aka fusion protein pierces through from the virus into the host cell and starts to draw the cell membrane and the viral membrane together to begin membrane fusion

Which of the following statements is FALSE?

- Maturation of the HIV virus occurs before the virus buds off from the host cell. - This is incorrect because the HIV virus maturation happens AFTER the virus buds off from the cell-

Know the role of the N/Np proteins in switching between production of mRNA and production of viral genomes.

- N protein is one of the proteins that are encoded from the 5 + mRNA that VSV synthesizes. It acts as an anti-terminator, once there are enough N proteins, RNA polymerase will stop creating the 5 separate mRNAs and instead create 1 full length Positive RNA strand. - Np protein binds to newly formed positive strand RNA so that host cell sequences aren't added to the 5 prime end, they also prevent the truncation of the 3 prime end, this allows the positive RNA to be translated into the correct negative strand RNA genome. This protein is used for influenza viruses.

Names of receptors and co-receptors for HIV infection

- Primary receptor: CD4 - Coreceptors: CCR5, CXCR4 - CCR5= Chemokine coreceptor

The names and functions of the three enzymes that are packaged in an HIV virus

- Reverse transcriptase: makes both strands of the double-stranded DNA that will ultimately be integrated into the host cell. - Integrase: nicks the host DNA and helps the HIV insert into the host chromosome. - Protease: Breaks up polyprotein chains allows for them to coalesce and form the mature structures that make up the final virion. - Tat, Rev, and Nef *specific to HIV*: Aid in transporting spliced RNA out of nucleus, Help dampen immune response, main function is to increase HIV pathogenesis

The major steps of viral replication for VSV and influenza

- Steps for ss negative RNA viruses follow the same replication scheme. - VSV (rabies) is unimolecular and influenza is segmented. - mRNA is shorter than the full genome, so there are differences in neative genomes replication processes: A. VSV: makes 5 mRNA segments then, using the increased N protein concentration generation from the proteins, can switch to genome making mode neg to positive to neg. N protein coats the negative strand. Influenza: makes multiple segments. Synthesizes each one and generates high concentration of NP proteins to generate genome copying.

Zika, single stranded positive RNA

- Symptoms: mild fever, skin rash, headache, muscle and joint pain, or conjunctivitis - Incubation period: few days to one week - Cell types infected : Cells surrounding the epidermis and dermis layer.Keratinocytes (epidermis), Fibroblasts (dermis), Dendritic cells (dermis). - Only 1 in 5 people get sick from Zika infection. - Causes mild symptoms, but in Brazil it widely circulated and resulted in significant increases in babies with abnormally small brains (microcephaly) Caused serious neurological deficits, seizures, & vision/hearing problems. - Prevention/Treatment: no vaccine- limit mosquito bites w/ bug spray & long sleeves Rest, fluid intake to prevent dehydration, and meds for fever and pain. - Transmission- arbovirus, transmitted via mosquitos. - Mosquitoes are vectors, meaning they only transport the virus. - Once a human is infected, it can reinfect another mosquito within the first week of infection as it is still found in the blood. - Similar "no dead end host" can be found in dengue and yellow fever where mosquitoes can become reinfected from a human - Other viruses that are transmitted through mosquitoes: dengue,zika,west nile fever, yellow fever and chikungunya. - Can also spread through sexual contact, blood transfusions, and pregnant woman can pass to their offspring - Family: Flaviviridae - Enveloped, non segmented RNA viruses - `Cells infected = keratinocytes, dendritic cells, and fibroblasts

Which of the following statements is true?

- The budding process is driven by the formation of matrix and capsid proteins forming a new viral particle underneath the cellular membrane where envelope proteins are embedded. - The protease cleaves the gag proteins within the viral particle to form the final capsid structure. - The gag-pol complex has viral enzymes bound to it for packaging. (protease, integrase, reverse transcriptase)

The difference between translation into one polyprotein (which is subsequently cleaved) and translation of individual proteins

- Usually one messenger RNA makes one protein. Not the case here because these have 1 message encodes for several protein - Viral enzymes cleave the polyprotein into individual proteins - Polyprotein cleavage occurs in a stepwise fashion for picornaviruses

The names and function of the viral surface glycoproteins hemagglutinin and neuraminidase and know which viruses express these glycoproteins

- Viruses that express these proteins: Influenza and Measles. - Neuraminidase: Cleaves the interaction between Hemagglutinin and sialic acid and allows budding out of the cell. - Hemagglutinin: Binds to sialic acid receptors at the beginning of virus entry.

Which of the following is a distinct step in the reverse transcription of retroviral RNA? Check all that apply.

-Initiation of positive DNA synthesis -template exchange

Steps of replication followed by Picornaviruses and Flaviviruses:

1. Begins by binding to the cellular receptor, entering through receptor- mediated endocytosis ( forms pore inside endicidic vesicle and releases nucleic acid into cytoplasm) 2. once the genome is released in cytoplasm, it is immediately translated by ribosomes. Their Genome is the mRNA. 3. RdRp ( enzyme makes copies of viral genome), then many copies of this genome are made. Some genome copies go back to ribosomes to be translated into more viral proteins, others go down and fuse with other viral proteins to form new viral particles. 4. Note copying of the genome occurs on the surface of membranous vesicles. Theory is that by being on the surface, it helps bring RNA and enzymes together so that everything that needs to be in one place for replication is in close proximity 5. All genome replication has a negative strand intermediate. When RdRp makes copy of positive sense of virus, a negative sense copy is the 1st copy that is made, then the polymerase can bind to negative sense copy and make a another positive sense copy of the RNA, and this new copy goes back to be used for translation or packaging into new viral particles1

Steps and timing of HIV infection and replication and the order in which they occur

1. HIV virus will bind to the CD4 cellular receptor causing a conformational change where the virus attaches to a coreceptor CCR5 which then allows for fusion of its envelope with the cell membrane. 2. The nucleocapsid remains within a subviral structure while the reverse transcriptase converts the viral RNA into ssDNA and then to dsDNA 3. The newly made dsDNA travels into the cell nucleus via integrase, where the integrase enzyme nicks the host cell chromosomes in order to insert the viral DNA into the chromosomes 4. The viral DNA is copied with normal cell replication (host RNA polymerase) and viral mRNA is created - this viral mRNA is made in the ER and is translated into envelope proteins by spliced mRNA and gag pol complex by unspliced mRNA. These proteins travel to the surface of the cell where it combines with capsid proteins nucleic acid to form a new viral particle. 5. The virus buds off the membrane as a immature virion 6. Protease then cleaves the gag pol complex to form individual proteins that are used to form the "cone" structure of the capsid.

Differences between simple retroviruses/lentiviruses and HIV in both genome structure and expression

1. HIV's capsid is shaped differently and it has more of a cone shape or conical shape 2. Lentivirus/retroviruses have nucleocapsid with icosahedral symmetry 3. HIV encodes more proteins that make it more complex: tat, nef, rev. 4. HIV encodes additional splicing mechanisms which means it can code for proteins utilizing very little space.

Infectious cycle of double stranded RNA viruses Reovirus.

1. Virus binds to receptor (receptor still unknown). 2. Virus taken up through endocytosis and endosome fuses w/ lysosome. 3. Virus can withstand the low pH of the lysosome because of its 2 shells. 4. Outer shell is eventually digested by the lysosome. 5. The subviral particle penetrates endosomal membrane into cytoplasm. 6. Synthesis of mRNA begins in the core. 7. mRNA made inside by rdrp and exit through turrets and enter the cytoplasm to be translated. 8. In cytoplasm, mRNA are encoded for proteins then new core molecules are assembled

ss (+) RNA genomes have structural elements in common with mRNA.

5' & 3' UTR 5' cap or Vpg (in poliovirus and norovirus)----> involved in translation 3' AAA tail (poly-A-tail)------>involved in replication of genome

The term for the one long protein that results from the translation of the picornavirus genome is

A polyprotein

Influenza A, B, and C

A: 8 RNA segments, subdivided by hemagglutinin and neuraminidase type (number), commonly infects humans and animals; mutates quickly. B: 8 RNA segments, less common, only infects humans, mutates more slowly, only a few H and N subtypes. C: 7 RNA segments, rarest, generally causes mild disease in children, least likely to mutate, infects humans and pigs, does not have hemagglutinin and neuraminidase, but rather hemagglutinin-esterase fusion protein to enter and exit cells.

Which detection method is best for early detection of HIV?

Antibody-Antigen tests that detect the virus in the blood

Reovirus:

Belongs to Reoviridae family & has 2 concentric shells. Most famous reovirus is rotavirus & causes severe childhood diarrhea Structure of virus vital in replication process & consists of whole intact viral particle, within that has infectious sub-viral particle & within that is the core. Within shells can find segmented dsRNA. Cannot use the + strand of this genome as mRNA so needs to make mRNA using viral enzyme, RdRp. Has protruding turrets coming out at each 5 fold axis of symmetry. Each segment gives rise to one mRNA and each mRNA encodes one protein mRNAs capped and polyadenylated and are complete genome copies so can be used to copy neg sense strand to make a new viral genome. All RNA is made in viral core. Replication Cycle: Binds to cell receptor which isn't known. Sialic acid can play a role in binding but not required. Take up through endocytosis and endosome fuses with lysosome. Lysosome has low pH but virus has two shells which makes it possible to undergo such extreme pH Outer shell gets digested away within lysosome & exposed subviral particle penetrates through endosomal membrane and gets released into cytoplasm mRNA synthesis can start in cytoplasm within core. With RdRp, makes multiple mRNAs which come out into cytoplasm through turrets. Are translated here. New core molecules can be assembled with RdRp and mRNA. Negative strand can be made. dsRNA Genome is created. Once a new core particle is made, it can bind with other viral proteins to make a complete viral particle which will exit the cell.

Viruses use a variety of mechanisms to escape from endosomes. As a result of lowered pH

Caliciviruses - forms a pore in endosomal membrane Adenoviruses - releases Protein (VI) that disrupts the membrane Dengue - changes conformation to form spike-like structures Influenza - exposes a fusion peptide Rhabdoviruses - envelope proteins change conformation

Ebola virus infects

Dendritic cells, macrophages and monocytes and by doing so disrupts the immune response and normal cellular processes.

Methods of diagnosis, detection, and treatment for HIV

Diagnosis: - Antibody test: Antibodies against HIV - Antibody/antigen test : recommended test, better at identifying early infection. Tests antibodies against HIV ans HIV itself (antigens). - RNA/DNA: test viral RNA and copies of viral RNA in DNA Treatment: Help live longer and healthier, reduce risk of transmission, Antiretroviral (ART) which is combination of medications (HIV regimen), slows HIV replication, helps immune system recover and fight other infections.

Influenza detection

ELISA antibody-based, but they need a lot of virus to detect and are not strain-specific.

RNA splicing is used to generate specific retroviral proteins

Env proteins

Which of the following lentivirus proteins are generated from a spliced RNA?

Envelope proteins

Ebola

Family: Filoviridae ss (-) RNA, enveloped, unimolecular Epidemiology Tracked with hemorrhagic fever Monkeys were sent to Germany and about 23% of the people died and became known as Marburg virus Known to be the cousin of Marbourg virus. 53% of the people in Sudan died and 88% of people died in Democratic of Congo These numbers were compared to the numbers with Germany Three strains known for outbreaks: Zaire, Sudan and Bundibugyo Zaire strain is known to cause the most fatality (responsible for the 2014 outbreak) In 2014, 28,000 were infected with a 62% mortality rate Mutation as studied through genetic sequencing helped to understand the prevalence and pathogenesis of ebola (theory) Characteristics and Known Proteins The genome is covered with nuclear proteins and VP30 Packages the RDRP Underneath the envelope is the matrix protein, VP40 Transcription messenger is similar to VSV One difference is that the viral proteins in ebola are encoded to antagonize or block the immune response, especially interferon response. VP24 and VP40 inhibit the interferon production and signaling The antibodies attacks the immune system, first hitting the dendritic cell NRK also gets infected and can't help to prevent the spread Neutrophils are not very impactful and is what causes internal bleeding Can also attack the liver very easily which causes organ failure and internal bleeding as well The spread is very fast through different parts of the body Last defense is the cytokine storm through SOS Could kill viruses but causes loads of damage to the blood vessels Leads to heavy dehydration as blood/fluid leaves the system entry mechanism Virus binds to cellular receptor Attachment receptor and entry receptors are unknown Could enter through pinocytosis Enter through endocytic pathway Escapes by fusing with the endosomal membrane and binds with NPC1 Capsid and nucleic acids are released in the cytoplasm. full, detailed steps of replication/anything unique? Viral/cellular enzymes if known. Other characteristics important to replication (envelope, size, stop codons in genome, etc.) Replication Cycle Similar to VSV when it comes to replication mRNA goes to the ER Rest of the mRNA are translated in the free parts of cytoplasm Viral capsid form in the cytoplasm and are transported to the cellular membrane by a liquid raft mechanism exit mechanism Cellular membranes proteins are embedded Full viral particle form and the virus is buds off host cell Transmission Contact with infected bodily fluids, contaminated needles/syringes. Vulnerable populations (epidemiological Not through food, aerosols and water Some form of zoonotic transmission (bats, monkeys or apes) Incubation time 2-21 days after infection Early symptoms fever, headache, muscle pain, stomach pain, vomiting, diarrhea Peak symptoms Hemorrhage, convulsions, rash, confusion, chest pain, severe diarrhea, coma, internal bleeding, death Cytokine storm causes the shock and leads to the killing of people

Influenza:

Family: Orthomyxoviridae - Coiled (-) ss RNA, 7-8 segments; contributes to genetic drift/shift. Genome replication occurs in the nucleus; unusual for RNA viruses. - Binds to sialic acid-containing cell surface protein or lipid.Enters via receptor-mediated endocytosis. Types that infect humans: A: 8 RNA segments - Can be subdivided in H and N protein; which have variations within themselves so they are identified by number: - Hemagglutinin - Neuraminidase - Most common infection of humans are (and animals): H3N2 - humans H1N1 - animals - Most common and most severe because it mutates H/N glycoproteins often. - Daughter viruses slightly differ from one another and parent. - Can change until it isn't recognized by immune system and attack someone who was immune to a previous strain. Genetic drift- explains why people could get sick year after year or even 2 in the same year. B: 8 RNA segments - Hemagglutinin and Neuraminidase proteins on surface - Less common. - Only affect humans. - Doesn't mutate as much as type A. - Only has a few NH proteins. C: 7 RNA Segments - 1 species - Least common, least mutations. - Causes mild illness in children. - Infects humans and pigs. - Uses Hemagglutinin Esterase- fusion protein to enter and exit cells. How it spreads: 1. Someone will sneeze or cough. 2. Spreads thousands of Droplets with the virus, can travel up to 6 ft. 3. Someone walks by and the droplets lands in the mouth or nose, or is inhaled. 4. They can also survive on surface for hours. Symptoms: - 1-4 days after infection they show - Headache - Fever - Runny nose - Sore throat and cough(last 2 weeks) - Symptoms get better after 1 week Complications: - Acute otitis media - Bronchiolitis - Croup - Sinusitis - Pneumonia- stap. Aureus and S. pneumiae High risk of complication include: -Babies less than 6 months More likely to have neurologic complications like: Encephalitis and Febrile seizures. - Reye syndrome- after taking aspirin the child can develop encephalopathy and liver disease. - Pregnant women - Adults over 65 - Chronic heart conditions- heart or lung disease - Contagious 1 day before symptoms show up to 1-2 weeks after. Diagnosis - Rapid influenza diagnostic tests - from nasal secretions( antibody based test- ELISA)- Elisa is not that sensitive (needs quite a bit of flu virus in system). - Detect in minutes. - Vary in reliability. - Can detect type but not strain. Viral culture (best one) - Growing and identifying. PCR - Detects RNA. Treatment mostly for high risk patients - Neuraminidase inhibitors( stops virus from exiting host cells). - M2 proton channel inhibitors- made of adamantane. a.Prevents viruses from replicating inside the host cell. b. However Virus M2 gene mutates often Allows it to become resistant to inhibitor. Prevention : -Vaccination trivalent - three strains predicted to dominate the coming season- based on previous season and data on current strains across globe(us and canada experience flu season opposite time as australia) - Trivalent inactivated Influenza vaccine (TIV): Killed virus that's injected into the muscle. - Live attenuated Influenza vaccine (LAIV): Weakened virus sprayed into the nose to infect epithelial cells.

Poliovirus, single stranded positive RNA:

Family: Picornaviridae Unique qualities: - Has a VPg protein for priming viral replication. - Similar to mRNA such as : poly-A-tail, 5 prime and 3 prime UTRs. - mRNA serves as their genome. Replication copied from book... - Entry mechanism: Binds to CD155 (receptor-mediated endocytosis). - Replication: Genome w/ VPg cap is released into cytoplasm.VPg is removed. ss positive RNA associates with cytoplasmic ribosomes.mRNA is translated into a polyprotein. Cleavage into individual proteins occurs during & after synthesis of the polyprotein. - Viral RNA synthesis proteins are transported to membrane vesicles.RNA synthesis occurs on the surfaces of membrane vesicles. - Positive strand RNA is transported to membrane vesicles and copied into double stranded RNA. - Newly-synthesized negative strands serve as templates for positive strand genomic RNA. - Structural proteins are formed by partial cleavage of the P1 polyprotein. Structural proteins associate w/ positive ssRNA (w. VPg attached);forms progeny virus particles. Exit mechanism: Lysis of host cell

VSV ss (-) RNA

Family: Rhabdoviridae (-) ss RNA, unimolecular, helical, packaged RdRp Disease: Rabies; can be caused by different Lyssaviruses. Entry mechanism: Receptor-mediated endocytosis - LDL Receptor Replication/Genome info: i. Helical nucleocapsid is released into the cytoplasm. ii. negative ssRNA is coated w/ Nucleocapsid (N), L & P (RdRp) proteins. RdRp catalyzes positive RNA synthesis. iii. Produces 5 mRNAs: G, M, N, P/C, & L. Capped + poly-A. - 1 mRNA = 1 protein. - Intergenic sequences cause RdRp to stop making mRNA. - Pauses, skips over → recognizes starting sequence and makes more mRNA M, P/C, N, & L: translated by cytoplasmic ribosomes G (env): translated by ER-bound ribosomes Control: - N protein coats negative genome. - As mRNAs + proteins are made, concentration of - N protein increases. - N protein coats new positive RNA. - N protein on negative strand prevents RdRp from stopping. positive strand RNA is made → negative RNA copy Exit mechanism: association of env proteins and genomic RNA → membrane budding

Rotavirus

Has dsRNA segmented #1 cause of severe diarrhea in infants & young children Diarrhea is severe due to the dehydration which kills. Rotavirus produces enterotoxin which is a protein that's toxic against the gut. Makes this diarrhea lethal. Symptoms include: non-bloody diarrhea, fever, vomiting Incubation period is 2 days and symptoms last for 1 week Vaccines available: 2 oral live attenuated vaccines which should be used in routine immunizations of all infants. 2 problems with vaccines include (1) reassortment(mix & match of different genome pieces to create different strains) & (2) intussusception(bowel telescopes into itself and can cause intestinal obstruction) Modes of transmission: fecal/oral route

HIV/AIDS:

Human Immunodeficiency Virus Type 1 (HIV) Family: Retroviridae genus: Lentivirus Enveloped, single stranded positive RNA → Baltimore Group VI (retrovirus) - 2 copies of RNA genome in nucleocapsid, nucleocapsid is conical shape (not icosahedral) - Must package reverse transcriptase RT (like other retrovirus) Entry: - Viral gp120 binds host CD4 (on immune cells, mainly T-cells). NEEDS HOST! Coreceptor: Either CXCR4 or CCR5 - After both are bound, fusion protein activates, membrane fusion occurs (loses its envelope). - Nucleocapsid degraded by host enzymes, genome in cytosol Replication: Overall Pathway: needs RT. ss positive RNA → ss DNA → dsDNA (all by RT). - dsDNA bound by integrase → taken to the nucleus → nicks host genome → integrates to form a provirus. - Everything from here on will be mediated by host proteins. Exit: - Transcription of viral DNA by host → envelope proteins travel to outer membrane from ER, integrate and wait to bud off. - Viral polyprotein gag-pol (contains capsid proteins) + RNA genome + key enzymes travel to outer membrane to meet envelope protein → bud off → protease cleaves → nucleocapsid forms inside envelope. - Note that the final virion is formed after everything has already bud off from host cell. Acquired Immunodeficiency Syndrome (AIDS) Hosts: Human Immunodeficiency Virus - human hosts Transmission: Spread through bodily fluids (mostly STD, some transmitted from needle sharing, & (rarely) blood transfusions before improved screening). Acute phase (12 weeks): flu-like symptoms. Chronic phase (several years): low T-cell count (if it is BELOW 200 T cell/mm^3 it is considered AIDS). - Being immunocompromised is very serious. This will lead to recurring bacterial/fungal infection, tumor, etc. 200-500 T-cells/mm3 (HIV infection): Lymphadenopathy, leukoplakia (oral white patches), oral candidiasis. < 200 T-cells/mm3 (AIDS):Fever, fatigue, weight loss, diarrhea, recurrent bacterial pneumonia,candidiasis, Kaposi sarcoma, primary lymphoma in the brain. Diagnosis & Treatment/Prevention: - Antibody test: detects anti-HIV antibodies. - Antibody/antigen test: detects both antibodies and HIV. Recommended 1st test. - RNA/DNA test: directly detects viral RNA & copies of provirus in DNA. - Recommended to follow positive antibody/antigen test with a 2nd test. - No cure, treatment includes a set of drugs 'antiretroviral therapy slows replication. - Same as prevention for other STDs (use protection during sexual intercourse)

Which of the following is a unique characteristic of Influenza replication in comparison to other RNA viruses?

Influenza RNA goes into the nucleus for transcription

Which viral enzyme is directly involved in incorporating HIV DNA into the host chromosome?

Integrase

The maturation process of HIV prior to infecting a new cell

Maturation process: Matrix and capsid proteins that are forming underneath the cellular membrane drives this budding process. As the virus builds, it begins to bud off the host cell. As it buds off, the interior of the virus structure begins to change. This occurs because the protease cleaves the gag proteins, which allows the particle to mature and allows the formation of the final capsid structure within the viral particle. ~All of this happens after the virus has budded off from the host cell.

Both VSV and influenza make mRNAs that are not complete copies of the genomic viral RNA (vRNA) and both use specific proteins to switch between making mRNA and positive RNA to serve as a template for genome replication.

N protein = vsv: Coats negative strand genome and binds to capsid proteins for helical symmetry. Produced N protein will prevent polymerase from stopping at intergenic sequences on negative, so you get whole replication in positive strand, which is then used to make a whole negative strand. N protein is an "antiterminator", NP protein = influenza. Works very similarly as antiterminator, but instead of preventing the polymerase from falling off at an intergenic sequence, these proteins bind to newly formed positive-strand RNA so the polymerase doesn't pull on that host sequence at the 5'end. And prevents losing 20 nt on 3' end

Influenza treatment

Neuraminidase inhibitors to prevent the virus breaking out of host cells. M2 proton channel inhibitors contain adamantane, prevent replication. Viral M2 mutates rapidly.

Which of the following viruses forms a pore in the endosomal membrane in order to release its nucleic acid into the cytoplasm? Check all that apply.

Norovirus and Poliovirus

Which protein is responsible for controlling the switch between making mRNAs and making a genome for Influenza virus?

Np protein

How subgenomic RNA is made

Occurs in the mechanism used by Alphaviruses: - So when the genome is being copied by RdRP, it not only makes a negative sense copy, but also makes a small mRNA that goes back to the ribosomes to make proteins that are not coded in the normal reading frame of the genome. - When the genome gets uncoded and released into cytoplasms, ribosomes will only translate part of the genome as they stop at a STOP codon. Even though ribosomes do not translate the latter part, there are still proteins in this region. - In order to make these proteins, the virus has to first make a negative strand. RdRp comes in and makes a negative stand but it's also able to recognize a specific sequence within this negative stand and it's able to make a positive copy of just the latter portion. This is the called the subgenomic mRNA NOT a genome.

Which ss negative RNA virus has a 100% mortality rate?

Rabies virus

Why translation must occur before replication

RdRp must be translated to then be used for replication. RdRp makes a negative RNA strand which can then be used as a template for the positive strand viral genome..44

Important structural features of Reoviruses and the role they play in replication.

Reoviruses have 2 concentric shells which hold RDRP and the viral genome: - Virion overall - Infectious sub-viral particle (ISVP): turrets that come out of the core at each 5 prime fold axis and behind which are the RDRP. - Core: where mRNA production occurs.

In which way is the retrovirus HIV, unlike other single stranded, positive sense, RNA viruses.?

Retroviruses encode an RNA transcriptase (RT) to convert their RNA to DNA

One day you find yourself sick with both diarrhea and vomiting. Since you've taken Virology, you know that you are likely infected with either Norovirus or Rotavirus. Which aspect of your illness or symptoms would give a good indication of which virus you were infected with?

Rotavirus is a pediatric disease, so I most likely have a Norovirus infection.

Preventative treatments available for these pathogens and any major complications associated with their administration.

Rotavirus vaccine = oral live attenuated vaccines. - side effects: mild GI symptoms and intussusception.

What is the most common mode of transmission for HIV

Sexual contact or intercourse

What molecule on the host cell does Influenza virus bind to?

Sialic acid

Fusion of the Ebola virus envelope with the endosomal membrane differs from other viruses that use this mechanism in what way?

The Ebola fusion protein binds specifically to the host receptor NPC1.

Which of the following steps is found in Dengue virus replication but not Poliovirus replication?

The viral RNA forms a circle prior to joining with the replication complex

T/F: Unlike single stranded negative RNA viruses, the mRNA of Reoviruses are full length copies of the viral genome.

True

Alphavirus, ss positive RNA

Unique qualities: - Subgenomic mRNA - Stop codon and they overcome this by going through a negative sense intermediate. Enveloped Virus Similar to mRNA in that: - 5 prime cap protein & 5 prime and 3 prime UTRs,, poly-A-tail. Replication: occurs on membranous vesicles - Entry mechanism: receptor-mediated endocytosis (RME) - They release their viral genome into the cytoplasm. - The ribosomes bind to the positive single stranded RNA and they begin to make viral proteins. - The first viral protein that is made is RdRp (nonstructural proteins that go on and replicate the genome on the membranous vesicle). When the genome is being copied by RdRp, this enzyme makes a negative sense copy of the entire viral genome and also makes a small positive strand of mRNA (a subgenomic mRNA) that will go back to the ribosomes to make proteins that are not encoded in the normal reading frame. - I.e. Initial translation wont translate the entire genome, so they need to go through a negative sense intermediate in order to access the coding region of the mRNA that the virus uses to replicate and make its structural proteins. - Once you have the making of the subgenomic mRNA, structural proteins (capsid and envelope proteins) are formed. - The enveloped proteins go through the natural secretory pathway of the cell and make their way to the cellular membrane. - The viral genome comes in and ultimately a new viral particle is formed and the virus buds off the cell.

Of the choices below, how does translation of VSV differ from translation of Poliovirus?

VSV translates each protein sequence individually while Poliovirus translates one long polyprotein that is ultimately cleaved by viral proteases.

What contributes to the cyclical nature of Norovirus outbreaks?

Viral evolution and the emergence of new viral strains

Non-Polio Enterovirus:

Viruses in this group: Echoviruses, Coxsackieviruses (A and B), and Enteroviruses - ALWAYS starts infection in GI tract and then spreads. - Skin: hand, foot, and mouth disease is caused by Cox A and this causes rashes in these regions with lesions. - Eyes: acute hemorrhagic conjunctivitis makes the eyes look blood shot and causes pain. - Heart: myocarditis and eventual heart failure is caused by Cox B. - CNS: meningitis of spinal cord is caused by Enteroviruses. - Brain: encephalitis. Acute flaccid paralysis is caused by Enterovirus D68. The incidence of AFP increased dramatically, especially in children and it takes months to years to recover from AFP. - Coxsackieviruses gained attention with their link to autoimmune disorders: Infection with Cox B virus has been linked to the onset of Type 1 Diabetes and Celiacs Disease, both of which are autoimmune.

The difference between HIV and AIDS and how it is determined when an individual has progressed to AIDS

When T cells get too low < 200 HIV = AIDS. This is characterized by persistent fever, fatigue, weight loss, diarrhea, HIV in blood increases significantly. - AIDS defining conditions: recurrent bacterial pneumonia, pneumocystis pneumonia, fungal infections candidiasis of esophagus, tumors Kaposi sarcoma, primary lymphoma of the brain.

Which of the following is NOT an area of the body that can be infected by non-polio Enteroviruses?

a. Liver

Antibody dependent enhancement causes subsequent Dengue infections to be more severe than primary infections with the virus

because it attaches to another receptor FC.

Which viral protein is used to bind to the CD4 receptor?

gp120

Which of the following statements is TRUE.

viral enzymes are responsible for cleaving the polyproteins of Flaviviruses