Exam 1 GMS 7133
How does +ssRNA retrovirus get enzymatic activity?
(+)RNA is copied into dsDNA by RNA-dependent DNAPolymerase called RT
Which group from the Baltimore Classification must bring in their own RDRP?
(+)ssRNA (-)ssRNA
Identify which virus replication is this? (Baltimore Classification): similar to + strand RNA presence of RT infects new cell, RT becomes active, converts + RNA to ssDNA ssDNA gets made into dsDNA follows same path as ssDNA virus +mRNA and + RNA made, proteins made, capsid made +ssRNA made, incorproated into new capsid/genome with RT
(+)ssRNA retrovirus replication
Identify which virus replication is this from the Baltimore Classification: +RNA basically the same as mRNA = sense strand can be immediately translated into proteins RNA dependent RNA poly is made (RDRP) binds incoming genome strands make antisense copy antisense template for sense strand, many copies some translated into proteins capsid made, + RNA inserted ex. Hep C, polio, SARS
(+)ssRNA virus replication
Identify which virus replication is this? (Baltimore Classification): cant be translated into protein bring their own RDRP to make + strand that acts as mRNA now able to amplify can make sense strand RNA which serves as a template for antisense strand proteins being generated from sense strand as well, capsid made
(-)ssRNA virus replication
What are some other major viral immune evasion strategies?
- Enter dormant state, avoiding immune recognition (i.e. herpesviruses, HIV) - Cell-to-cell spread to avoid antibody-mediated clearance (no longer limited to enveloped viruses) [quasi-enveloped] - Antigenic evolution/escape [genetic drift for influenza)
Wha happens when herpes virus binds to Tap and Tapsin?
- blocks the peptide editing function of tapasin and ERp57 - Binds to MHC I and retains it in the ER
What gappens when Adenovirus binds to TAP and tapasin?
- interferes with the interaction between tapasin and MHC I - excludes MHC I from the PLC - Binds to MHC I and retains it in the ER
What is the particle assembly process for covid?
1) N binds RNA = NC 2) M and E insert into ER membranes 3) S inserts into intracellular and plasma membrane 4) M interacts with N and S and initiates budding 5) Budding occurs into ERGIC 6) Viral glycoproteins processed in Golgi after budding 7) Release occurs upon vesicles fusion with PM
Virus genetic diversity results from what two main factors?
1) the exceptionally large numbers of progeny viruses produced in an infected host 2) the high mutation rate of viruses
What are the general stages of virus infection?
1. Adsorption 2. Entry 3. Uncoating 4. Early genes 5. Replication 6. Late genes 7. Assembly 8. Packaging 9. Release
Why would VP35 want to present IRF-3/7?
1. Interacts with the kinase domains in IKK and TBK I preventing their ability to phosphorylate target proteins 2. Interacts with E2 and E3 enzymes that are responsible for a process referred to as sumolyation. VP35 causes sumoylation of IRF-3/7 prematurely leading to decreased IFN expression during an active viral infection
What is the process of Phagocytosis ?
1. Phagocytes Binds to pathogen 2. The pathogen is ingested by a Phagocyte 3. The fusion of lysosomes with the phagosome 4. Antigen presentation via MCH class II ( present to T helper cell)
What do viruses lack that they must gain from their host? 1. enzymes that produce basic chemical _______ _______ 2. enzymes that generate usably ________ 3. enzymes, tRNAs, and/or ribosomes that direct ______ _______ 4. membranes that ______ and _______ key molecules
1. enzymes that produce basic chemical building blocks 2. enzymes that generate usable energy 3. enzymes, tRNAs, and/or ribosomes that direct protein synthesis 4. membranes that concentrate and localize key molecules
What does recombination do that point mutations do not?
1.Create combinations of mutations that would have a low probability of occurring all at once (e.g., multi-drug resistance) 2.Juxtapose viral genomes with limited homology, or intertypic recombination (e.g., attenuated poliovirus recombines with enterovirus to restore virulence) 3.Transduce sequences from nonhomologous genomes at a low frequency (e.g., retroviral transduction of host sequences)
whats the order in which they are most active CD8+, virus, Antibodies, Type I interferon, NK cells
1st: Type I interferon->NK cells -> virus -> CD8+ -> antibodies
If phages were lined up head to tail, how long would they be?
2 x 10^8 light years
Match :progressive/escaped/vagrancy hypothesis 1. increase in complex city and emergence of translation 2. Autonomous replication or selfish cellular genes 3. Reductive evolution, loss of relation and obligate parasitism
2. Autonomous replication or selfish cellular genes
Quiz: Each triangular face of a capsid is usually made of ____ proteins.
3
Match: Regressive/regression/degeneracy hypothesis 1. increase in complex city and emergence of translation 2. Autonomous replication or selfish cellular genes 3. Reductive evolution, loss of relation and obligate parasitism
3. Reductive evolution, loss of relation and obligate parasitism
How many ATP are needed to make a single peptide bond
4 ATP
How many structural domains does an S Glycoprotein have? Name them and their functions.
4 domains from N to C-terminal: S1 = globular head S2 = more conserved sequence, fusion-promoting, external stalk Transmembrane domain Cytoplasmic domain
Coronaviruses cause ____% of human respiratory infections usually acute and self-limited disease
5-30%
More than ____ new viruses have emerged since 1988
50
What is the function of N protein? 50-60kD phosphoprotein Binds viral RNA, forming ____ ribonucleoprotein complex binds cellular ____ interaction with ____ protein drives formation of particles only coronavirus protein known to localize to ____ and thought to inhibits cytokine production antagonizes interferon
50-60kD phosphoprotein Binds viral RNA, forming helical ribonucleoprotein complex binds cellular membranes interaction with M protein drives formation of particles only coronavirus protein known to localize to nucleus and thought to inhibits cytokine production antagonizes interferon
What symmetry do icosahedral shapes exhibit ?
5:3:2 symmetry
Icosahedral capsids have exhibit 5:3:2 symmetry, what shape does it make? ?-fold axes = point of the star ?-fold axes = side that joins each face together ?-fold axes = middle of each triangular face no matter how you rotate each axis = _____
5:3:2 symmetry 5-fold axes = point of the star 2-fold axes = side that joins each face together 3-fold axes = middle of each triangular face no matter how you rotate each axis = identical
How many proteins form the simplest icosahedral capsids? ___ identical proteins ___ proteins = 1 complex 1 complex self-assembles with other complexes to form ___ faces of icosahedral shape
60 identical proteins 3 proteins = 1 complex 1 complex self-assembles with other complexes to form 20 faces of icosahedral shape 3x20 = 60
How effective is the Moderna and Pfizer vaccine?
95%
What is a quasi-enveloped virus? A virus that is only partially wrapped in a lipid bilayer. A virus that expresses its glycoprotein(s) in some virions but not others. A classically nonenveloped virus that exits a host cell in an exosome or other cellular vesicle. A nonenveloped virus that is wrapped in two proteinaceous capsid layers.
A classically nonenveloped virus that exits a host cell in an exosome or other cellular vesicle.
What is the purpose of phylogenetic tree?
A phylogenetic tree is a diagram that represents evolutionary relationships among organisms. Phylogenetic trees are hypotheses, not definitive facts. The pattern of branching in a phylogenetic tree reflects how species or other groups evolved from a series of common ancestors.
What are the two viral genome function/needs?
A)Replication in order to make progeny virus B)Make mRNAs to make viral proteins
What is the consensus sequence of a viral quasispecies? A. The average nucleotide at each position of a viral genome. B. The sequence of the virus after treatment with an antiviral drug. C. The sequence that researchers agree upon as the wild-type sequence. D. The sequence of the most fit viral genotype under a given selection pressure.
A. The average nucleotide at each position of a viral genome.
The most important enzyme for RNA virus replication is the RDRP (RNA-dependent RNA polymerase). In order for negative strand (-) RNA viruses to replicate in a newly infected cell, they must [note, this could have more than 1 correct answer]: A. express RDRP immediately after entry B. hijack host RDRP C. first make a (+)RNA genome copy D. incorporate RDRP into the viral particle E. first replicate the (-)RNA genome
A. express RDRP immediately after entry C. first make a (+)RNA genome copy D. incorporate RDRP into the viral particle
When a B cell binds to its specific epitope it becomes ____
Activated
When a T cell binds to its specific epitope on an antigen presenting cell it becomes ______
Activated
What is paracrine activity?
Activity on non infected cells, interferon tells non infected cells that there is a virus around
SARS-CoV binds to ACE2
Adaptation of a virus to a homologous receptor of a new host species may require very few amino acid substitutions at the large receptor-binding interface
SARS-CoV binds to ACE2 Adaptation of a virus to a homologous receptor of a new host species may require very few amino acid ______at the large receptor-binding interface
Adaptation of a virus to a homologous receptor of a new host species may require very few amino acid substitutions at the large receptor-binding interface
______ immunity; highly specific cells, expand and clear infection
Adaptive
Adaptive Response time: Specificity: Recall:
Adaptive Response time: Days, weeks Specificity: highly diverse Recall: memory
Afferent lymphatic vessels feed out/into lymph nodes Effertent lymphatic Vessels flow out/into of lymph nodes
Afferent lymphatic vessels feed INTO lymph nodes Effertent lymphatic Vessels flow OUT of lymph nodes (DRAIN)
What are some Large-scale changes in virus ecology introduced by humans
Air travel Dams Irrigation Air conditioning Blood transfusion Massive urbanization Day care centers Poliomyelitis incidence Changes in sex habits, drug abuse Deforestation Long-distance transport of cattle, chickens, etc. Changes in wildlife migration patterns
Viral RNA blocks ____ activation to induce apoptosis
Akt
How might virus infection lead to increased level of ATP? Stimulation of glucose uptake Increase glycolysis Increase oxidation of fatty acids Increased utilization of glutamine All of the above
All of the above
Virus infection greatly impacts cellular metabolic processes, including: Glucose metabolism Fatty acid synthesis Citric acid cycle All of the above
All of the above
Which of the following factors have contributed to the emergence of new viruses in recent years? Air travel Climate change Massive urbanization Deforestation All of the above
All of the above
Which of the following is a strategy used by a virus to block MHC class I antigen presentation? Block peptide transport across TAP. Block the movement of MHC class I complexes from the ER to the plasma membrane. Stimulate endocytosis and consequent degradation of MHC class I complexes from the plasma membrane. All of the above
All of the above
Antigen presentation to the T cell by a _____ or _____ is critical for induction of adaptive immune response
Antigen presentation to the T cell by a macrophage or DC is critical for induction of adaptive immune response
Wat are some examples of fomites?
Any inanimate object in which an organism can stick to it and survive, then spread to another host (Ex: door handle or water fountain). Found a lot on cruise ships.
What is an example of lethal mutagenesis as a natural form of antiviral defense?
ApoBac proteins, retroviruses Get packaged with genome and causes hyper mutation
At the MOST detailed level, classification schemes take into account the genetic relatedness of individual viruses by comparing their: viral ____ nucleotide sequences viral ____ amino acid sequences
At the MOST detailed level, classification schemes take into account the genetic relatedness of individual viruses by comparing their: viral genome nucleotide sequences viral protein amino acid sequences
B cells are also lymphocytes - when activated they can become ____ cells, which are factories for _____
B cells are also lymphocytes - when activated they can become plasma cells, which are factories for antibodies
What class is Covid-19 a part of? A) Alpha-CoV B) Beta-CoV C)Gamma-CoV D) Delta-CoV
B)Beta-CoV
Bacteriophage capsids the ____of the bacteriophage is icosahedral the ____ of the bacteriophage is helical
Bacteriophage capsids the head of the bacteriophage is icosahedral the tail of the bacteriophage is helical
What is the most widely used classification system for viruses? ____________ It takes into account ______ and use of ___________.
Baltimore classification system It takes into account virus genome structure and use of reverse transcriptase
What animals are considered to be the true reservoir for covid?
Bats
What animals do we think we got covid from?
Bats and anteaters
Ebola VP35 blocks IFN induction via several mechanisms, name 3
Binds to dsRNA Interacts with PACT Prevents phosphorylation of IRF-3/7
A major effect of many viruses on host cell proteins is to: Block tRNA binding to amino acids Block translation of mRNA into proteins Block acidification of protein complexes Block tRNA signal transduction
Block translation of mRNA into proteins
Where are all immune cells generated?
Bone marrow and thymus
Which are the primary lymphoid organs?
Bone marrow and thymus
What is 472C mean? 472U?
C is wld type U is vaccine strain
What is NOT an example of a genetic bottleneck? A. Continual passaging of single virus plaques. B. Small numbers of viral genotypes are transmitted from one host to another in a respiratory droplet. C. A chemical mutagen like ribavirin is applied to a quasispecies to increase the genetic diversity. D. Small numbers of viral genotypes are introduced into a host during viral transmission from an insect bite.
C. A chemical mutagen like ribavirin is applied to a quasispecies to increase the genetic diversity.
____ Cells; Cells that are the quarterbacks (tell cells what to do )of the immune system - the ramp up or shut down most of the other cells
CD4+
____ Cells; Cells that are cytotoxic, they are armored to kill and destroy virus infected cells
CD8+
What are the two major types of T cells?
CD8+ T cells and CD4+ T cells
Coronavirus Which is the disease itself? The virus that causes the disease?
COVID-19 and SARS-COV-2
What is a protein coat encoded by the virus?
Capsid
Why would it be beneficial for virus to remove the cap?
Cell mRNA degradation proteins removed or delocalized in virus infected cells
why would the host cell form stress granules?
Cells take the actively translating viral mRNA and put them in these stress granules These are not translated Lets put all of the RNA in these granules and shut them down until things get better
What are the secondary lymphoid organs?
Cervial lymph nodes Inguinal lymph nodes Axillary lymph nodes Spleen MALT = mucosal associated lymphoid tissue
Describe how Poliomyelitis incidence has increased
Children were breastfeed and people lived away from other Post 1900 we saw the rise in urbanization and sanitation issues Massive increase in paralysis attributed to polio infections
What is a cis acting DNA variant? Trans?
Cis-acting variants are found close to the target genes and trans-acting variants are located far from the target genes, often on another chromosome.
What animals are considered to be the intermediate host for covid?
Civet cat
What class are these viruses a part of? Families: Herpesviruses (HSV-1, CMV and EBV), Pox (Vaccinia), Papillomaviruses (HPV),Adenoviruses (many subtypes), Polyomaviruses
Class I: dsDNA viruses
What class are these viruses a part of? Families: Parvoviridae(AAV), Anneloviruses
Class II: ssDNAviruses
What class are these viruses a part of? Families : Example of Human virus is Reoviruses(Rotavirus)Segmented 11 dsRNAs
Class III: dsRNA viruses
What class are these viruses a part of? Families: Flaviviruses (HCV), Polioviruses, Coronaviruses
Class IV: (+) strand ssRNAviruses:
What class are these viruses a part of? Families: Orthomyxoviridae(Influenza, FLU), Filoviridae (Ebola), Arenaviridae(Lassa)One more category: segmented vs. non-segmented genomes (Influenza has seven)
Class V: (-)ssRNAviruses
What class are these viruses a part of? Families: Retroviruses (HIV), plus HTLV (only 2 human Retroviruses known)
Class VI: +ssRNA retrovirus
What class are these viruses a part of? Family: Hepadnaviridae; Hepatitis B Virus (HBV)
Class VII: dsDNA plus RNA viruses
What factors likely contributed to the global spread of West Nile?
Climate changes affecting both the natural avian host as well as the insect vector in this case Affecting birds: Warmer winters and a longer frost-free season would affect birds migration patterns as well as the survival rate of their offspring Affecting mosquitoes: rising temp, changing rain patterns, and a higher frequenting of extreme weather events influence the aquatic habitant availability of mosquitoes and reproduction rate of the insect
What is the purpose of the N protein?
Coats RNA genome itself
Compared to primary responses, memory responses are: 1. Lower/Higher frequency of antigen-specific cells (~1000x) 2. Slower/Faster (due to changes in gene expression) 3. Develop effector cells less/more efficiently (ie, requires lower Ag doses)
Compared to primary responses, memory responses are: 1. Higher frequency of antigen-specific cells (~1000x) 2. Faster (due to changes in gene expression) 3. Develop effector cells more efficiently (ie, requires lower Ag doses)
average nucleotide at each position; may or may not exist in the population
Consensus sequence
Consequences of selection on a quasispecies Consequently, the product of selection after replication is a new, ____ population that shares only the selected ______
Consequences of selection on a quasispecies Consequently, the product of selection after replication is a new, diverse population that shares only the selected mutations
How can RNA get variability other than mutations?
Copy-choice recombination
Coronavirus mRNA production 1)Leader sequence(65-98nt) at the beginning of each mRNA is _____ to sequence at 5' end of the genome 2)7-18nt transcriptional regulatory sequence (TRS) is the only homology to genomic leader found ____ of leader in full-length genome 3) Generated through ____ transcription during negative-strand synthesis
Coronavirus mRNA production 1)Leader sequence(65-98nt) at the beginning of each mRNA is identical to sequence at 5' end of the genome 2)7-18nt transcriptional regulatory sequence (TRS) is the only homology to genomic leader found downstream of leader in full-length genome 3) Generated through discontinuous transcription during negative-strand synthesis
Cycle of infection Entry -> ____ site -> shedding or Entry -> ____ site -> spread (local lymphatic, neuronal, blood(viremia))-> _____ sites -> shedding
Cycle of infection Entry -> Primary site -> shedding or Entry -> Primary site -> spread (local lymphatic, neuronal, blood(viremia))-> Secondary sites -> shedding
What are the main pieces of evidence arguing that civet cats are NOT the SARS-CoV reservoir? A. Free-ranging civets out in the wild are not infected with SARS-CoV. B. Civets in the markets of the Guangdong regions of China were infected with SARS-CoV. C. When civets are infected with SARS-CoV experimentally, they develop symptoms. D. A and C E. All of the above
D. A and C
DNA or RNA + Capsid protein =
DNA or RNA + Capsid protein = nucleocapsid
What is the basic virus structure?
DNA or RNA + Capsid protein = nucleocapsid Nucleocapsid = naked capsid virus Nucleocapsid + lipid membrane, glycoproteins = enveloped virus
DNA or RNA + Capsid protein = nucleocapsid -> _________
DNA or RNA + Capsid protein = nucleocapsid -> naked capsid virus
What are nucleic acids?
DNA, RNA, ss, ds
How can viral proteins interfere in gene expression?
Degrades the transcription factors that are needed Splicing and mRNA export is inhibited, host cell RNA is degraded as well Reduce cellular mRNA. It does this to reduce the competition for translation
Direct detection of virus •_______-visualization of virus proteins (particles or antigens) •____-antibody detection of virus proteins (particles or antigens) •________-visualization of virus particles •_____-molecular detection of virus nucleic acids (genome or transcripts)
Direct detection of virus •Immunofluorescence-visualization of virus proteins (particles or antigens) •ELISA-antibody detection of virus proteins (particles or antigens) •Electron microscopy -visualization of virus particles •PCR-molecular detection of virus nucleic acids (genome or transcripts)
Which of the following is a consequence of viral proteins modifying signal transduction pathways to promote replication? Poliovirus inhibition of transcription by RNA pol II Herpes simplex virus protein blocking pre-mRNA splicing cleave Disruption of actin filaments to allow endocytosis Initiation of mRNA degradation by viral proteins cleave
Disruption of actin filaments to allow endocytosis All of the rest are cleaving, not signaling
You need ____ to overcome a selective pressure in the cell
Diversity
how does viral replication still occur if the cap binding protein is degraded/modified
Doesn't need it, many viruses don't use a cap Has.
How do you define a quasispecies- phenotypically?
Drug resistance, dead, attenuated, resistance to antibody
Which of the following are selective pressures that could drive virus evolution? A. Drying out after being shed into the environment. B. A virus-specific antibody response C. Treatment of an infected host with an antiviral drug D. Low pH of the stomach E. All of the above
E. All of the above
Growth of _____is strongly attenuated in IFN-competent cells
EBOV/VP35KRA
EBOV/VP35KRA is highly attenuated in guinea pigs and protects against challenge with ____
EBOVwt
Interference with MHC I peptide loading and egress of MHC I from the ____
ER
How does poliovirus remodel cellular organelles?
ER and golgi is gone
What is ERAD?
ER-associated degradation of MHC class I Normally functions to target misfolded proteins in the ER for ubiquination by the protreasome
Viruses recruit _____ complexes to facilitate their budding process
ESCRT
How does Muller's ratchet analogy work?
Each round of error-prone replication works like a ratchet, "clicking" forward as mutations accumulate at every replication cycle The accumulation of deleterious mutations in a small population is irreversible and can be catastrophic
What two general stages of virus infection have the most variability between viruses?
Early Genes and replication
What is the rationale for suspecting zoonotic transmission in SARS?
Early SARS patients in Guangdong Province exposed to live wild game animals in markets; these had highly genetically related viruses (99%)
____ causes outbreaks of viral hemorrhagic fever with high fatality rates
Ebola
_____: blocks phosphorylated STAT1 from localizing to the nucleus
Ebola virus VP24
Ebola virus VP35 protein is responsible for blocking interferon _____ VP40 and VP24 are responsible for blocking interferon ____
Ebola virus VP35 protein is responsible for blocking interferon induction VP40 and VP24 are responsible for blocking interferon signaling
What is the viral cycle of infection?
Entry Primary site replication spread within the host shedding transmission
What are the basics of coronavirus? (Enveloped/Naked), ______-sense RNA viruses The _____ genome of all RNA viruses Unique replication strategy results in a high frequency of _____ Mature virions bud at _____ membranes Infect many species including _____, causing a range of diseases Since the occurrence of SARS, have become considered as '_____pathogens'
Enveloped, positive-sense RNA viruses The largest genome of all RNA viruses Unique replication strategy results in a high frequency of recombination Mature virions bud at intracellular membranes Infect many species including humans, causing a range of diseases Since the occurrence of SARS, have become considered as 'emerging pathogens'
How do dsDNA viruses get mRNA synthesis?
Enzymatic activity Host pol II dsDNA-dependent RNA polymerase
How do ssDNA viruses get mRNA synthesis??
Enzymatic activity Host pol II dsDNA-dependent RNA polymerase
How does (+)ssRNA virus get enzymatic activity?
Enzymatic activity:Viral RNA-dependent RNA polymerase
What Three theories to explain the origins of viruses is being described? viruses were once part of the genetic material of host cells but escaped cell control and later evolved by pickpocketing genes via horizontal gene transfer (HGT) HGT is believed by some scientists to be the predominant force shaping many viral genomes.
Escape, or progressive or vagrancy, hypothesis
What will happen to a naked capsid if I add ethanol to it? What about bleach?
Ethanol: Nothing Bleach: Kill/Inactivate
What is unique about bacteriophage capsids?
Exhibit both icosahedral and helical
If MVBs(multivesicular bodies) fuse with plasma membrane, they release _____ and other luminal contents into extracellular space
Exosomes
______; Extracellular vesicles that function in cell-to-cell communication
Exosomes
T.F All viruses can undergo reassortment.
False
T.F The case fatality rate of COVID-19 is the same in every country across the globe.
False
T.F The viral genotype that replicates the fastest is always selected (i.e. survival of the fittest).
False
T/F: Children are more susceptible to severe disease outcomes following SARS-CoV-2 infection.
False
T/F: coronaviruses mutation rates are a lot higher than most RNA viruses
False Coronaviruses mutation rates are a lot lower than most RNA viruses
T/F: In some CoV, S protein fusion activity requires proteolytic cleavage at one site
False In some CoV, S protein fusion activity requires proteolytic cleavage at one site or two sites
T/F: Coronaviruses only infect humans
False Infect mammals and birds
T/F: M protein is required for budding virons; targeted to ER Membranes
False M protein is required for budding virions; targeted to Golgi Membranes
T/F Natural reservoir animals usually carry the virus frequently and show symptoms
False Natural reservoir animals usually carry the virus frequently but are asymptomatic
T.F +ssRNA must package their own RDRP and its first step is to make a - strand
False, RNA genome is (+) strand mRNA and first step is translation of viral proteins including RNA-dependent RNA polymerase
Consequences of selection on a quasispecies T.F The large number of progeny produced are complex products of selective forces outside the host
False, The large number of progeny produced are complex products of selective forces inside the host
Consequences of selection on a quasispecies T.F Viral infections are initiated by a single virus
False, Viral infections are initiated by a population of particles, not a single virus particle
T.F The virome are only viruses that infect bacteria?
False, human cells and other human resident life forms (bacteira)
T: if you want a high confidence in detecting human viruses, you would use indirect methods
False, use direct methods like virus isolation>genome detection>antigen detection Use indirect for easy access
T.F Naive T cells have highly unspecific T cells receptor (TCRs) on their surface
False, Highly specific
T.F Virus-infected cells produce small numbers of progeny
False, Virus-infected cells produce large numbers of progeny
T.F Viruses cannot target every single step in the IFN induction pathway
False, Viruses have evolved to target every single step in the IFN induction pathway
T.F Viruses can interfere with IFN induction or IFN signaling, but not both
False, can interfere with both at the same time
T.F Measles virus infection reduces measles antibody
False, increases measles, but decreases antibody diversity
T.F all dsDNA viruses use host cell to make mRNA
False, there is an exception PoxvirusesHave no access to nucleus and have their own enzyme complexes to make mRNA
True or False: RNA is not well protected in a helical naked capsid virus
False. RNA is in the middle so it is surrounded and protected by proteins
Tell me about the structure of filovirus ?
Filoviruses (e.g., Ebola, Marburg) are filamentous, enveloped, negative-sense RNA viruses
T/F: polymerase(RdRp complex) jumps to the 3' end to copy leader
Flase polymerase(RdRp complex) jumps to the 5' end to copy leader
Following virus entry, virus is taken up by macrophages and iDCs, which mature and migrate to the local _____ to initiate an immune response
Following virus entry, virus is taken up by macrophages and iDCs, which mature and migrate to the local lymph node to initiate an immune response
Viruses are obligate intracellular parasites because they lack: Genes that are required for protein synthesis Genes that encode proteins A lipid envelope A nucleus
Genes that are required for protein synthesis
______; After each passage the fitness gets lower. Extreme selective pressures on small populations that result in loss of diversity
Genetic bottlenecks
Genetic bottlenecks; • Continual passaging of _____ viral plaques: After 20-30 cycles many virus populations are barely able to grow, markedly less _____ than original Environment is theoretically ____ so only apparent selection is imposed by passaging a small population of viruses
Genetic bottlenecks; • Continual passaging of single viral plaques: After 20-30 cycles many virus populations are barely able to grow, markedly less fit than original Environment is theoretically constant so only apparent selection is imposed by passaging a small population of viruses
Word bank: Genetic drift, genetic shift diversity arising from copying errors and immune selection, may occur each time a genome replicates
Genetic drift
Word bank: Genetic drift, genetic shift diversity arising after recombination or reassortment, relatively rare
Genetic shift
How do you define a quasispecies- genetically?
Genotype being sequence analyze the various HCV variants according to the prevalence major populations (>10% quasispecies) intermediate populations (10%-1% quasispecicies) minority populations (>1% quasispecicies)
Explain how SIV overcame its bottleneck
Genotypes that overcame the bottleneck involved in moving from a chimpanzee host into a human host Each primate has its own form of SIV There are three HIV-1 groups referred to as M, N, and O that are all through to have originated from three separate chip to human transmissions
How many groups are in the Baltimore classification system and what are their differences?
Group I = dsDNA Group II = ssDNA Group III = dsRNA Group IV = + strand RNA Group V = - strand RNA Group VI = retroviruses w/ RT Group VII = ss/dsDNA w/ RT
Which group in the Baltimore classification system uses reverse transcriptase?
Group I = dsDNA Group II = ssDNA Group III = dsRNA Group IV = + strand RNA Group V = - strand RNA Group VI = retroviruses w/ RT Group VII = ss/dsDNA w/ RT
Which group in the Baltimore classification system uses both ss/dsDNA?
Group VII = ss/dsDNA w/ RT
Group-specific accessory proteins produced from ______ Generally: 1) nonessential in ____ 2) No significant homology to proteins in NCBI databases 3)Play roles in vivo subverting ____ response 4) Some are packaged, considered structural now
Group-specific accessory proteins produced from sgmRNAs Generally: 1) nonessential in vitro 2) No significant homology to proteins in NCBI databases 3)Play roles in vivo subverting immune response 4) Some are packaged, considered structural now
How does dsDNA retroviruses make mRNA synthesis?
HBV: host polII
How does +ssRNA viruses get mRNA synthesis?
HCV: genome is mRNA and template for (-) strand which is needed to make more mRNA and new genomes
How does +ssRNA retrovirus get mRNA synthesis?
HIV: host polII from integrated provirus
MHC are called "____" molecules in humans
HLA
All white blood cells are generated from an ____
HSC(Hematopoietic stem cell)
What is an example of how herpes virus affects metabolism?
HSV has shorter reproduction cycle, need more nucleotide precursors to synthesize viral DNA
A major advantage of enveloped viruses is that they are: Resistant to bleach Resistant to the First Order Resistant to acidic environments Harder for the immune system to get rid of
Harder for the immune system to get rid of
Sin Nombre virus, it is a hanta virus whose natural reservior is the deer mouse that's known to live in the praries of these states. Explain how Climate changes impacted its viral emergence?
Heavy rain favored growth of the nuts that these rodents eat, so the number of deer mice increased dramatically leading them to migrate to UT, CO,AZ and NM near humans The virus was then passed from rodents to humans through aerosolized exposure to infected urine and feces
What shape is the nucleocapsid
Helical
What virus targets ERAD(associated degradation of MHC class I )?
Herpesvirus US I I
Herpesvirus US11: - Inserts into ER membrane and ER luminal domain interacts with ____ HC - TM domain recruits ____-1 which associates with other members of the dislocation complex - Together with E2 conjugating enzymes UBE2J2 and UBE2K, MHC I HC becomes _____ on cytosolic domain and extracted from membrane and is degraded by the proteasome
Herpesvirus US11: - Inserts into ER membrane and ER luminal domain interacts with MHC I HC - TM domain recruits Derlin-1 which associates with other members of the dislocation complex - Together with E2 conjugating enzymes UBE2J2 and UBE2K, MHC I HC becomes ubiquitinated on cytosolic domain and extracted from membrane and is degraded by the proteasome
What two viruses bind to TAP and tapasin ?
Herpesvirus US3 and adenovirus E3-19K
Virus infection can establish different patterns of infection with respect to longevity and virus replication kinetics. These patterns are termed 1) Acute infection, 2) Chronic Infection, and 3) Latent infection. Which viruses cause which kind of infection? Please pair the following viruses with their typical infection pattern: Acute, Chronic, or Latent. Herpesvirus HIV Hepatitis B Influenza
Herpesvirus: latent HIV: Chronic Hepatitis B: chronic Influenza: acute
Muller's ratchet: Small a sexual populations decline in fitness over time if the mutation rate is ____
High
Rank from high confidence/specificity to easy access/opportunity Genome detection, serology IgM, virus isolation, antigen detection, serology IgG
High confidence: virus isolation>genome detection>antigen detection>serology IgM>Serology IgG: easy access
High fidelity genome replication is atypical for RNA viruses 1)High mutation rate of most RdRp lacking ______ activity caps the size of the RNA virus genome at ~15kb, yet coronaviruses are ~30 kb 2) Increased fidelity provided by a virally encoded ______(ExoN;nsp14) [ proofreading enzyme] 3)Their mutation rates are a lot _____ than that of most RNA viruses
High fidelity genome replication is atypical for RNA viruses 1)High mutation rate of most RdRp lacking proofreading activity caps the size of the RNA virus genome at ~15kb, yet coronaviruses are ~30 kb 2) Increased fidelity provided by a virally encoded exonuclease (ExoN;nsp14) [ proofreading enzyme] 3)Their mutation rates are a lot lower than that of most RNA viruses
How can DNA get variability other than mutations?
Homologous recombination recombination and reassortment
In 1859, Australians imported European rabbit so they could hunt them; no natural predators so rabbits reproduced to astronomical levels. In 1950s - released myxoma virus into the environment, is extremely fatal in European rabbitsIn the 1st year, 99.8% of exposed rabbits died In 2nd year, 30% of exposed rabbits died. WHY?
Host changed •Rabbits evolved to become more resistant to myxoma virus Virus changed •Virus evolved to kill fewer rabbits and to extend the life of lethally infected rabbits •Resulted in virus that could survive the winter in its host and spread in spring mosquitos = NOT ACTIVE, SELECTION OF VIRUSES THAT DIDN'T KILL
Viral evolution occurs in concert with host evolution, what does mean?
Host recognized virus if wears a blue sweater. Virus has mutation to change to purple sweater. Host cant recognize virus.[virus winning] Host gets new update(mutation) and can now recognize virus with purple sweater [host winning] cycle continues
How do ssDNA viruses get genome replication?
Host-encoded encoded polymerases (polymerase delta and epsilon)
What is an issue with the Progressive/escaped/vagrancy hypothesis
Hypothesis doesn't explain the complex capsid structure of virions nor does it explain sequences that are unique to viruses and not found anywhere in cells
What was the hypothesis of the 472-C study?
Hypothesis: The failure of some batches of type 3 OPV in WHO monkey neurovirulence test is due to presence in vaccine preps of 472-C mutants
ER-associated degradation (ERAD) of MHC class ___
I
What are the two types of things IFN can do?
IFN induction IFN signaling
IFN _____; production of interferon itself IFN _____; signaling pathway that culminates in the production of the ISGs
IFN induction; production of interferon itself IFN signaling; signaling pathway that culminates in the production of the ISGs
What activates paracrine activity?
INF
How do infections that spread by these routes escape Muller's ratchet?
If you pool several plaques, you avoid the ratchet by increasing the diversity As long as you have enough diversity in the population, you can survive Facilitated also by recombination and reassortment Could produce a healthy virus
In NON-infected cells, ____ IFN binding induces ISGs that act to _____ infection at multiple stages
In NON-infected cells, paracrine IFN binding induces ISGs that act to prevent infection at multiple stages
In a _____ virus population you have a high population that have all of these genetic variants capable of overcoming different selective pressures In a population that had a _____ event occur you will see a less diverse population. Many of the mutations here are shared across entire quasipecies and its less diverse and less fit
In a orignal virus population you have a high population that have all of these genetic variants capable of overcoming different selective pressures In a population that had a bottleneck event occur you will see a less diverse population. Many of the mutations here are shared across entire quasipecies and its less diverse and less fit
In infected cells, ____ IFN binding leads to ISGs(interferon stimulated genes) which block _____ infection
In infected cells, autocrine IFN binding leads to ISGs(interferon stimulated genes) which block ongoing infection
What is a mechanism of shedding transmission?
Indirect contact Direct contact
PRR recognition of virus infections results in IFN𝑎a/𝛽β responses that do all of the following except: Induce ISG responses in both non-infected and infected cells Induce T cell-mediated killing of infected cells Activate paracrine antiviral responses in non-infected cells Activate autocrine antiviral responses in the infected cells
Induce T cell-mediated killing of infected cells
No innate immune response =
Infection is not controlled
Time course of infection; host response? Infection without spread? Infection with spread?
Infection without spread: day 1 prodrome, day 2-6 symptoms at primary site, day 6 to 12 healing Infection with spread: day 1-8 prodome, day 8-12 symptoms at secondary site
What type of pattern of disease does; Influenza hepatitis b/c virus herpes
Influenza; acute hepatitis b/c virus; chronic herpes; latent
why would HCMV particles want to increase fatty acid synthesis(malonyl-CoA or FAS)?
Inhibition of malonyl-CoA or FAS reduces yield of HCMV particles
____ immunity; non-specific cells, act early to slow the infection
Innate
Innate Response time: Specificity: Recall:
Innate Response time: minutes, hours Specificity: limited, fixed Recall: identical to primary
What kind of cells are differentiated from the myeloid stem cells?
Innate cells macrophages and dendritic cells
Concept: There are two waves of the immune system, what are they?
Innate immunity and adaptive immunity
How many days for the Host immune response to kick in? Innate(interferon): Adaptive(cellular/antibody): Inflammatory(immunopathogenesis:
Innate(interferon): day 1 -5 Adaptive(cellular/antibody): day 5 -8 Inflammatory(immunopathogenesis: day 8 to 12
What is an example of Inhibition of cellular pre-mRNA processing by viral proteins?
Interfere with splicing and removing introns If you interfere with splicing that transcript doesn't get out of the nucleus Splicing marks it for export remember Want to keep cellular RNA in the nucleus
eIF2 is important for translation; Why would the host cell want to turn on EIF2 if it senses a virus?
It wants to turn off translation because the host senses that there is a virus
Although Ebola and Marburg viruses are highly related filoviruses and both block _____, their mechanisms of inhibition are _____
Jak- STAT signaling, distinct
KSHV kK3: - Is an E3 ubiquitin ____ -Recruits E2 conjugating enzyme UBE2D2/3 ,resulting in monoubiquitination of HC (but mono-ub not sufficient for ___) - UBE2N is then required to facilitate ubiquitin chain elongation, signaling clathrin-mediated ___ - Ultimately leads to lysosomal ____
KSHV kK3: - Is an E3 ubiquitin ligase -Recruits E2 conjugating enzyme UBE2D2/3 ,resulting in monoubiquitination of HC (but mono-ub not sufficient for internalization) - UBE2N is then required to facilitate ubiquitin chain elongation, signaling clathrin-mediated endocytosis - Ultimately leads to lysosomal degradation
What does the use of multiple proteins in a capsid structure allow for? ____ capsids poliovirus = ___ faces, __ DIFFERENT proteins per face
Larger capsids poliovirus = 60 faces, 3 DIFFERENT proteins per face
Like retroviruses some retrotransposons encode a ____ enzyme and an ____ These elements can thus be transcribed into RNA, RT into DNA and then integrated into a new location in the ____
Like retroviruses some retrotransposons encode a RT enzyme and an integrase These elements can thus be transcribed into RNA, RT into DNA and then integrated into a new location in the genome
What is an envelope?
Lipid membrane provided by the host
What kind of vaccine is OPV?
Live attentuated that has been [assed on monkeys
What ways can a virus spread?
Local lymphatic neuronal blood(viremia)
Where is the place where adaptive responses are generated?
Lymph node Spleen MALT (through mucosal tissues)
What is the most abundant envelope protein of virus?
M Protein
The APC "presents" antigen to the T cell in the context of an ____ molecule
MHC
MHC I binds to ____ T cells MHC II binds to ____ T cells
MHC I binds to CD8 T cells MHC II binds to CD4 T cells
How do viruses compare to bacteria?
MUCH smaller first discovered because of their size, used a filter to screen out bacteria and found pathogenic particles still present = virus
Budding of enveloped viruses often uses _____ biogenesis machinery
MVB (multivesicular bodies)
A common feature of icosahedral virus capsids is that they are: Made of triangular faces in multiples of 20 Made of host proteins Made of 4-5 viral proteins Made of lipid envelopes
Made of triangular faces in multiples of 20
What are some constraints on evolution?
Maintain functions of proteins Maintain specific sequences required for replication Maintain complex capsid structures - size, space, symmetry Maintain interactions with host cell machinery Maintain proper modification of host defenses
What do the subgenomic RNA make?
Makes structural and accessory proteins
______; prevents tyrosine phosphorylation of the receptor- associated kinases, Jak1,Tyk2, STAT1 and STAT2; likely through a direct inhibition of Jak1 although mechanism remains undefined
Marburg VP40
Measles; Using the same cohort as the previous study and sequencing the B cell receptor gene: - The naïve B cell pool was _____ reconstituted after measles infection - Immune memory to previously encountered pathogens was ______
Measles; Using the same cohort as the previous study and sequencing the B cell receptor gene: - The naïve B cell pool was incompletely reconstituted after measles infection - Immune memory to previously encountered pathogens was compromised
Production of large quantities of virus particles places high demands on host cell biosynthesis systems Nucleotides, amino acids, fatty acids
Metabolism
Middle East respiratory syndrome (MERS) coronavirus Located in: Does not/does appear to spread efficnetly human to human Cases result from direct contact with _____ ___ are likely to be reservoir host for MERS
Middle East respiratory syndrome (MERS) coronavirus Located in: Saudi Arabia Does not appear to spread efficnetly human to human Cases result from direct contact with camels Bats are likely to be reservoir host for MERS
What happens over time to HBV replication when there is an initiation of antiviral therapy? What happens if there is a discontinuation of antiviral agents?
Mutant virus develops fitness for active replication (resistant virus). There is a virologic breakthrough of the resistance virus. Over time there will be a re-emergence of wild type virus after discontinuation of antiviral agent
What two things can an HSC(Hematopoietic stem cell) Differentiate in depending on the signals?
Myeloid stem cell (innate) Lymphoid stem cell (Adaptive or NK[innate])
Which is the only coronavirus protein known to localize to nucleus and thought to inhibits cytokine production?
N Protein
Describe the basic structure of coronavirus? N: M: S: HE: E:
N: Nucleocapsid M: Membrane glycoprotein S: Spike glycoproteins HE: Hemagglutinin-esterase glycoprotein (not all CoVs have this spike) E: Small envelope glycoprotein
What are the differences between naked capsid and enveloped viruses?
Naked Capsid = resistant to drying, heat, detergents, acid Enveloped virus = sensitive to drying, heat, detergents, acid
What types white blood cells can be differentiated by a lymphoid stem cell?
Natural killer cell; innate T cell; Adaptive B cell; Adaptive Plasma cell; adaptive
Nucleocapsid + _______, ______ = enveloped virus
Nucleocapsid + lipid membrane, glycoproteins = enveloped virus
What type of parasites are viruses?
Obligate intracellular
One advantage of a helical naked capsid is that because it is a tube, it can vary the _____ of the genome
One advantage of a helical naked capsid is that because it is a tube, it can vary the length of the genome
What is the order and family of coronavirus?
Order: Nidovirales Family: Coronaviridae
The Baltimore virus classification system is based on the mechanisms by which viruses generate mRNA from their genomes. We also learned that some virus families need to deliver replication enzymes during viral infection. This applies to which virus family? Parvoviruses Adenoviruses Herpesviruses Orthomyxoviruses
Orthomyxoviruses
The host cell senses virus infection through intracellular molecules called ____
PRR (pattern recognition receptors)
Explain how HIV transmission is an example of a bottleneck:
People who are chronically infected with HV have an extreme diverse HIV-1 population in their blood Some viruses from the blood will see the genital tract where the resulting population is less diverse and it is also dominated by a few closely amplified variants that are more fit in this host environment This is one bottleneck Viruses in this donor genetical tract are present in transmission fluids like vaginal mucus and semen so they will be the initial infecting viruses of a new host The vast majority of these viruses in the transmission fluid don't penetrate the genital or the rectal mucus of the recipient so this is yet another bottleneck Typically when a systemic infection is established after sexual exposure to HIV-1 the initial viral population in the recipient blood will be genetically homogenous as you can see here This is because it was established from a single viral genotype which is referred to as the transmitted or the founder virus that was able to replicate in the recipient genital tract This is the 3rd bottleneck Eventually, these individuals will display an extremely diverse HIV population in their blood just like the donor did back here but importantly the quasispecies will be very different on these two individuals because of the bottlenecks encountered along the course of transmission
Where is tap located?
Peptide binding site of MCH I
What is the PLC?
Peptide loading complex A PLC assembly consists TAP1 and TAP2, ERp57, the MHC-I, and the chaperones tapasin and calreticulin.
Macrophages and dendritic cells are ______ that take up viruses
Phagocytes
____ = antigen presenting cells (APCs)
Phagocytes
What does PKR do?
Phosphorylation of EIF2 system You need two PKr molecules that are bound to a single double stranded RNA that will activate each other and then the active PKr will go on to phosphorylate EIF2 and shut down translation
What is the importance of phylogenetics in studying viral transmission?
Phylogenetics is important because it enriches our understanding of how genes, genomes, species (and molecular sequences more generally) evolve.
What are the pros and cons of enveloped virus?
Positive: -does not need to kill cells in order to spread - may require both humoral (antibody) and cellular (t cell) immune responses Negative: -can not survive GI tract -must stay wet during transmission -transmission in large droplets and secretions
What are the pros and cons of naked capsid virus?
Positive: -retain infectivity on drying -survive well on environmental surfaces -spread easily via fomites -can survive acidic environment of GI tract Negative: -MUST kill host cells to release mature virus particles -Antibody response may be sufficient to neutralize infection
Potential ___ and _____ polymerase switch mechanism. Protease jumping is facilitated by genome _____.
Potential cis and trans polymerase switch mechanism. Protease jumping is facilitated by genome folding.
What is an exception for Class I: dsDNA viruses?
Poxviruses Have no access to nucleus and have their own enzyme complexes to make mRNA
Naïve T cells only become activated when they encounter their specific antigen: Presented by another T cell in the lymph node Presented by an APC on an MHC molecule Presented by stem cells in the bone marrow Presented by an APC on a lipid membrane
Presented by an APC on an MHC molecule
Why would VP35 want to interact with PACT?
Prevents it from interacting with RIG-1 and performing its normal enhancing activity
early phage of disease in which symptoms are mild or non specific
Prodrome
Where are MCH I produced? Where does it go? Who recognizes it?
Produced in ER Shuttle to Plasma membrane Recognized by CD8 T cells
Production of nonstructural proteins: 1)ORF1a and ORF1b translated from incoming _____RNA 2) 1ab is produced by ribosomal _____(-1) mechanism involving pseudoknot in RNA 3) Both polyproteins are ____-cleaves into 16 active products 4)One ____ protein are made, they replicate the genome
Production of nonstructural proteins: 1)ORF1a and ORF1b translated from incoming genomic RNA 2) 1ab is produced by ribosomal frameshift (-1) mechanism involving pseudoknot in RNA 3) Both polyproteins are cis-cleaves into 16 active products 4)One nonstructural proteins are made, they replicate the genome
retroviruses replication supports which of the Three theories to explain the origins of viruses
Progressive/escaped/vagrancy hypothesis
Which of the following is NOT one of the four major host cell processes altered by virus infection? Metabolism Remodeling of cellular organelles Protein folding Signal transduction
Protein folding
clouds of related elements that behave almost (quasi) like a single type of molecule (species)
Quasispecies
How is RDRP different from RT?
RDRP: RNA to mRNA RT: RNA to DNA
Does Moderna and Pfizer use DNA or RNA in their vaccines?
RNA
How do dsRNA viruses get enzymatic activity?
RNA-dependent RNA polymerase which makes 11 (+) strand mRNAs that also serve as template for (-) strand RNA synthesis
_____ = a situation or process that is perceived to be deteriorating or changing steadily in a series of irreversible steps
Ratchet
Mutations that ablate dsRNA binding activity do not impact its ____ co-factor activity; nor do they impair the ____ inhibition activity
RdRp, kinase
What Three theories to explain the origins of viruses is being described? This one suggests that viruses were once small cells that parasitized larger cells, and that over time the genes not required by their parasitism were lost.
Regressive ,or reduction or degeneracy, hypothesis
Regressive/regression/degeneracy hypothesis states that Viruses were initially self ____ but as they evolved to parasitize or ____ on a cell they lost genes encoding functions they no longer needed because they could simply rely on the cell machinery to do these task for them
Regressive/regression/degeneracy hypothesis states that Viruses were initially self replicating but as they evolved to parasitize or depend on a cell they lost genes encoding functions they no longer needed because they could simply rely on the cell machinery to do these task for them
What viral manipulation is being desired below? Glycolytic pyruvate kinase recruited into viral replication complex to generate ATP for RNA synthesis Recruits polymerase into a vesicle Pulls enzyme into this isolated vesicles to make ATP for the virus
Remodeling of cellular organelles
How does HCV remodel cellular organelles?
Repurposes membrane in the cell Derived form the ER Maturation of virus particles occurs
What are the routes of shedding/transmission?
Respiratory GI(oral/fecal) Urogenital Skin
What three diseases does coronavirus cause?
Respiratory, gastrointestinal, and CNS diseases
_____ elements actually make up a large proportion of the human genome and they can move within the genome via an RNA intermediate
Retrotransposons
SARS (severe acute respiratory syndrome)
SARS triphasic pattern of disease Week 1: prodromal phase -fever, non-productive cough, sore throat, diarrhea and myalgia Week 2: shortness of breath with continued fever and diarrhea; respiratory status of some patients continues to decline Week 3: acute respiratory distress; considered likely due to cytokine storm- Deaths occured4-108 d after onset-Shedding from respiratory tract peaked at d 10-Shedding from GI tract common-Severity of disease correlated with age -mortality 50% for patients over 60
SARS-CoV binds to _____ Of the 220 amino acids that make up RBD of the S protein, only 4 differ between human epidemic and civet cat strain-_____x difference in binding affinity to human ACE2 14 residues in RBD contact 18 residues on ACE2- only 2 differ between human and civet
SARS-CoV binds to ACE2 Of the 220 amino acids that make up RBD of the S protein, only 4 differ between human epidemic and civet cat strain-1000x difference in binding affinity to human ACE2 14 residues in RBD contact 18 residues on ACE2- only 2 differ between human and civet
Ebola virus VP24 blocks _____ nuclear localization
STAT
How does covid-19 replicate in the cell?
See attached picture
What does the coronavirus life cycle look like?
See attached picture
What is the mechanism of SARS-CoV-2 entry?
See attached picture
If you want to examine biological role of viral quasispecies, group wanted to test the effect of enhanced RdRp fidelity, what can you test?
See if Poliovirus with a single amino acid change in RdRp, G64S, displayed increased fidelity
How does DNA vaccine work? RNA?
See picture attached
all the possible combinations that a genome can have (e.g., total # combinations for 10kb genome is 410,000due to 4 nucleotide options per base); most sequence space is empty because mutations are lethal (puts constraints on viral evolution)
Sequence space
Which of the following is indirect detection of virus? Serology Immunofluorescence ELISA Electron microscopy PCR
Serology
_____ -molecular detection of virus nucleic acids (genome or transcripts)
Serology
What is the function of M protein? Short N-terminal domain _____of envelope, spans membrane 3 times and large C-terminal domain INSIDE envelope the primary component of internal ____-shell viral membrane unusually ____, probably because the C-terminal region of M forms an extra internal layer MOST _____ envelope protein _____for budding Required for budding of virions; targeted to ____membranes
Short N-terminal domain OUTSIDE of envelope, spans membrane 3 times and large C-terminal domain INSIDE envelope the primary component of internal core-shell viral membrane unusually thick, probably because the C-terminal region of M forms an extra internal layer MOST ABUNDANT envelope protein REQUIRED for budding Required for budding of virions; targeted to Golgi membranes
_____ transduction; Cells must sense their environment and respond appropriately
Signal
What four things does a virus depend on from a cell?
Signal transduction Gene expression Metabolism Remodeling of cellular organelles
How does a virus get taken up by a cell?
Signaling via Pi3K which will promote actin microfilament to be loosed up for endocytosis
The innate immune response: Is highly antigen specific Slows down early infection Is typically initiated a few days after infection Destroys infected cell "virus factories"
Slows down early infection
What is the function of E protein? Small/Large Naked/envelope protein hydrophobic/hydrophilic required for ____ of virions, also localizes to ____membranes Function not understood but has ___ channel activity and induces ____
Small envelope protein hydrophobic required for budding of virions, also localizes to Golgi membranes Function not understood but has ion channel activity and induces apoptosis
So a virus infects a cell, makes ds RNA through replication and the ds RNA is sensed by ____, Pk2 is phosphorylated and activated and will phosphorylate ____ to stop translation to prevent the virus from using its systems
So a virus infects a cell, makes ds RNA through replication and the ds RNA is sensed by PK2, Pk2 is phosphorylated and activated and will phosphorylates EIF2 to stop translation to prevent the virus from using its systems
What do the majority of SARS-CoV-2 vaccine target?
Spike protein
What is the genome structure of coronavirus?
Starting from 5' Polymerase (H/E) S E M N 3' then 2 - 8 additional group-specific ORFs capped/polyadenylated
Regressive/regression/degeneracy hypothesis
States that viruses may have originated via a reductive process Viruses were once small cells that parasitized larger cells Its supported by the discovery of giant viruses with similar genetic material to parasitic bacteria Its well accepted that some obligate intracellular bacteria like chlamydia which now require cellular processes actually evolved from free living ancestors
Progressive/escaped/vagrancy hypothesis
States that viruses originated through a progressive process Viruses could have evolved from bits of DNA or RNA that escaped from the genes of larger organism So mobile genetic elements or pieces of cellular genetic material capable of moving within a genome gain the ability to exit one cell and enter another
Consequences of selection on a quasispecies ________; A rare genome with a particular mutation may survive a selection event, and this mutation will be found in all progeny genomes (e.g., drug resistant genome)
Survival of the fittest
What does the activation of Pi3K-mTor do?
Survival vs cell death Viruses want to block cell death and upregulate transcription -> translation
Where do T cells start and finish developing? B cells?
T cells: start in Bone marrow and finish in thymus B cells: start and finish in Bone marrow
What are some examples of PRR (pattern recognition receptors) ?
TRL = toll like receptor CLRs = C-type lectin receptor NLRs = NOD receptors RLRs = RIG-I-like receptor
What does the induction of ISG( interferon-stimulated genes) go?
Tells non infected cells to shut down
The bottleneck arises by restricting further viral ____ to the progeny found in a single plaque • A few thousand progeny viruses derived from a single ____ virus
The bottleneck arises by restricting further viral replication to the progeny found in a single plaque • A few thousand progeny viruses derived from a single founder virus
What does virus replication strategy depend on?
The form of the incoming genome ds vs ss RNA vs DNA + vs - strand reverse transcriptase present
The induction of ISGs in an non-infected cells is called the "_____"
The induction of ISGs in an non-infected cells is called the "antiviral state"
The _____ system is a system of vessels that provides a means for the immune system to regionally survey the body for foreign antigens
The lymphatic system is a system of vessels that provides a means for the immune system to regionally survey the body for foreign antigens
The nonspecific innate immune response - critical to control the _____ stages of infection and the extend of pathogen replication and spread
The nonspecific innate immune response - critical to control the early stages of infection and the extend of pathogen replication and spread
The specific adaptive immune response - critical for specific _____ of the pathogen, protecting the host from excessive damage
The specific adaptive immune response - critical for specific clearance of the pathogen, protecting the host from excessive damage
What is an issue with the Regressive/regression/degeneracy hypothesis
This doesn't explain why even the smallest of cellular parasites doesn't resemble a virus in any way
What supports the Virus-first, or virus-early, hypothesis
This is supported by the idea that all viral genomes encode for proteins that don't have cellular homologs
What happens when the autocrine or paracrine signaling is activated?
This triggers a JAK-STAT signaling cascade that upregulates hundred of genes that will be resistant to viral infection and better able to block virus replication These genes are known as interferon-stimulated genes or ISGs Many directly interfere with the viral replication processes
What does herpes virus protein HSHV kk3 do?
Tiggers endocytosis of the MHC I complex after it has reached the cell surface
Why would VP35 want to bind to dsRNA?
To sequester its own danger signal so it cant be recognized by PPT like RIG-1 and MDA5
What cells within the host does the virus infect? Influenced by cellular receptors, intracellular molecular restriction, route of infection and spread
Tropism
What is the term: Capability of a virus to infect a distinct group of cells in the host
Tropism
Consequences of selection on a quasispecies T.F Linked but unselected mutations can get a free ride
True
T.F Although ebola is a -ssRNA, there is a short period of time when it is replicating that it produces dsRNA
True
T.F Antibodies cant kill a virus when it is wrapped inside of an exosome
True
T.F Coronaviruses have one glycoprotein that is responsible for BOTH receptor binding and membrane fusion.
True
T.F DNA polymerase Reverse Transcriptase also synthesizes ssDNA into dsDNA
True
T.F Different viral mechanism have evolved to inactivate PKR pathway
True
T.F Each person makes tens of millions of different TCRs
True
T.F Ebola virus inhibits the production and the signaling of type I interferon (IFN).
True
T.F Every B cell makes a different antibody - and every antibody binds to a different epitope
True
T.F For viruses, survival of the flattest apply more than survival of the fitness
True
T.F G64S high-fidelity mutant regains neurovirulence when artificially expanded
True
T.F Immune cells act as a trojan course for measles
True
T.F Measles virus infection reduce antibody diversity
True
T.F RNA viruses have more mutations than dsDNA viruses
True
T.F Since no host function makes (+) strand mRNAs from dsRNA the virus replicase must be packaged into virions
True
T.F Viral evolution occurs in concert with host evolution
True
T.F any cell can express type I interferon when infected by a virus
True
T.F for dsRNA viruses since no host function makes (+) strand mRNAs from dsRNA the virus replicase must be packaged into virion
True
T.F when ebola has a dsRNA intermediate, it is a PAM
True
T/F Intermediate host have symptoms
True
T/F: Jumping(RdRp complex) promotes recombination between different parental genomes
True
T/F: Nonstructural proteins come first then structural and accessory proteins in coronavirus
True
T/F: The dromedary camel is the intermediate host for MERS-CoV.
True
T/F: The spike (S) protein of coronaviruses is responsible for fusion of the viral and host membranes.
True
T/F: the N protein antagonizes interferon
True
T/F: Viral membrane of coronavirus is unsusally thick
True viral membrane unusually thick, probably because the C-terminal region of M forms an extra internal layer
T.F -ssRNA must package their own RDRP and its first step is to make a + strand
True, Since no host function makes (+) strand mRNAs from -strand RNA the virus replicase must be packaged into virions
Two point mutations in VP35 (VP35KRA virus) abrogate its dsRNA binding activity without altering the ____ of VP35 or affecting its polymerase ____ function
Two point mutations in VP35 (VP35KRA virus) abrogate its dsRNA binding activity without altering the structure of VP35 or affecting its polymerase cofactor function
Ebola is capable of replicating to extremely high levels in infected hosts, reflecting Ebola antagonism of antiviral defenses particularly ____ ____
Type I IFN
What happens after the PRR is activated and promotes transcription and translation of type I interferon?
Type I interferon cytokines are then released from the producing cell where they bind to the type I interferon receptor
Type I interferon is a group of ____ encoded by a single interferon beta and multiple interferon ____ genes. Can be potentially antiviral
Type I interferon is a group of cytokines encoded by a single interferon beta and multiple interferon alpha genes. Can be potentially antiviral
How does VA RNA I work?
VA RNA binds to one molecule of PKR (and one only!) so PKr cannot be activated and there is no phosphorylation= protein synthesis continues Without VA RNA adenovirus cannot replicate efficiently
Ebola virus VP24 blocks STAT nuclear localization, how ?
VP24 binds KPNA at the same site that is used by STAT1. It outcompetes STAT1 and thus prevents access of STAT1 to KPNA. This prevents its movement into the nucleus
Why cant STAT go to the nucleus with ebola virus?
VP24 blocks STAT1 from going into the nucleus and thus preventing signaling of type 1 interferon
Ebola ____ blocks IFN induction via several mechanisms
VP35
What does the virus use instead of a cap?
VPg protein for internal initiation Also uses eIF2G footprint Virus doesn't need a cap! Ribosomes bind directly without a cap
Cellular protein synthesis is inhibited by virus infection and that is replaced by virus translation
Viral Inhibition of cell translation
How does -ssRNA replication get enzymatic activity?
Viral RNA-dependent RNA polymerase
mixture of viruses (cloud/swarm/spectra) genetically similar but non-identical as a result of mutation, recombination and reassortment
Viral quasispecies
How do dsDNA viruses get genome replication?
Virally encoded DNA polymerase
How do dsRNA viruses get mRNA synthesis?
Virion packaged Replicase
How does -ssRNA replication get mRNA synthesis?
Virion packaged Replicase- strand is template to make+strand which serves as mRNA and template for synthesis of-strand genomes
eIF2 is important for translation; Why does the virus want to block EIF2?
Virus blocks EIF2 which then will prevent it from stopping translation = translation continues (similar to HPV)
How does dsDNA retroviruses make enzymatic activity?
Virus encodes RTMakes first ssDNA from (+) RNA and then dsDNA from ssDNA
Xrn1 is a host defense mechanism that will chew up viral RNA. What has the virus evolved to get around this?
Virus has evolved to use this stem loop to inactivate Xrn1 and will promote apoptosis
What is an example of signal transduction?
Virus infections can change signaling to promote replication Ex: signaling pathway to sense nutrients in the environment, and will turn on to take it in, if something is wrong it will activate cell death
How does a virus manipulate the citric acid cycle (TCA)?
Virus pulls citrate to make fatty acids and puts in glutamine to complete the process and make some energy as well
What Three theories to explain the origins of viruses is being described? viruses predated cells and contributed to the rise of cellular life. A significant proportion of all the viral genomes encode for genetic sequences that lack clear cellular homologs. Presence of such virus-specific sequences provides support to their unique origin.
Virus-first, or virus-early, hypothesis
Why are stress granules bad for the virus?
Viruses try to prevent formation out of these stress granules which would otherwise shut down protein translation
What are the pros and cons of an enveloped virus? Positive: -does not need to ___ cells in order to spread - may require both _____ (antibody) and _____ (t cell) immune responses Negative: -can not survive ____ -must stay ____ during transmission -transmission in large _____ and secretions
What are the pros and cons of an enveloped virus? Positive: -does not need to kill cells in order to spread - may require both humoral (antibody) and cellular (T cell) immune responses Negative: -can not survive GI tract -must stay wet during transmission -transmission in large droplets and secretions
What are the pros and cons of naked capsid virus? Positive: -retain infectivity on _____ -survive well on environmental _____ -spread easily via ____ -can survive acidic environment of ____ Negative: -MUST ____ host cells to release mature virus particles -Antibody response may be sufficient to ____ infection
What are the pros and cons of naked capsid virus? Positive: -retain infectivity on drying -survive well on environmental surfaces -spread easily via fomites -can survive acidic environment of GI tract Negative: -MUST kill host cells to release mature virus particles -Antibody response may be sufficient to neutralize infection
What is the argument against wild game animals as a reservoir?
When free-ranging animals of these species were examined, no viruses similar to SARS-CoV were found Infection of these species cause symptomatic disease uncommon in a reservoir host
How is a drop in fitness is caused by genetic bottleneck?
When you take a plaque you are taking a sampling of viruses present in the parent population Only some will be infectious because mutations are introduced by chance and many of them will be lethal to the viruses ability to replicate The surviving variants after you go through a bottleneck or you pick a virus plaque then replicate and become the predominant members of now this low complexity quasispecies
Virus-first, or virus-early, hypothesis
Where viruses were the first replicating entities Proposed that viruses existed in a pre-cellular world as self replicating units or referred to as replicons Overtime these units could have become more organized and complex and eventually evolving enzymes for synthesis of membranes and cell walls Resulting in the formation of cells Viruses predate or coevolved with their current cellular host Viruses evolved from complex proteins and nucleic acid before cells first appeared on earth So viruses could have contributed to the rise of cellular life
_____ blood cells that are most important for virus infections
White blood cells that are most important for virus infections
Without Interferon where is STAT located? with interferon treatment?
Without: Cytoplasm With interferon: Nucelus
Does virus taxonomy follow biological taxonomy? What is the order?
Yes Order>Family>subfamily>genus>species
What is a virion?
a complete, infectious virus particle
At a more detailed level, what do virus classification schemes take into account? *a. ____of nucleic acid genome (DNA/RNA) *b. _____of nucleic acid (single or double, plus or minus) c. ______of nucleic acid (linear or circular genome) d. _____ of capsid (icosahedral, helical, none) e. presence or absence of an ________
a. type of nucleic acid genome (DNA/RNA) b. Strandedness of nucleic acid (single or double, plus or minus) c. Topology of nucleic acid (linear or circular) d. Symmetry of capsid (icosahedral, helical, none) e. presence or absence of an envelope
What are the four effect viruses have on cells?
abortive infection, lytic infection, persistance, transformation
When naïve B cells bind virus particles or virus antigens and get CD4 T cell help, they become ....
activated, differentiate and expand
The mutant virus (cant block interferon) does replicate in animal and elicits an adaptive immune response but its severely impaired in ____ replication because of its inability to block interferon induction
acute,
How do you spread a virus through indirect contact?
aerosoles fomites
What was the goal of the 472-C study?
an 472-C be detected in vaccine preparations and can its abundance in vaccine lot be correlated with results of monkey neurovirulence test
Many, if not all, viruses can ____ IFN induction
antagonize
A cell expressing ISGs is said to be in an _____state
anti-viral
Naive B cells have ____ on their surface
antibodies
Nonenveloped viruses can escape _____- mediated clearance by being released in exosomes
antibody
Plasma cells secrete ____ for decades
antibody
T cell activation and differentiation requires ____ to the T cell
antigen presentation
Immunofluorescence is a useful means to detect viral particles or viral_____ in tissue or cell samples A. envelopes B. DNA C. antigens D. antibodies E. RNA
antigens
Type I interferon induces an ____ state
antiviral
Climate changes impact the vector and reservoir species of ____
arboviruses
What is Virscan? What study was it used on
assay that tracks antibodies to thousands of pathogen epitopes in blood used to see how severe the measles infection was on kids
what is the accepted reservoir host of SARS
bat
Ebola virus VP24 and Marburg virus VP40 proteins ____ IFN signaling
block
what do ISGs or interferon-stimulated genes do?
block specific steps in viral replication
Further variability introduced by recombination. Resultant viruses have sequences from _____ parental viruses
both
When a species goes through an event that suddenly and significantly reduces its population. The individuals that survive have greatly reduced genetic diversity compared to the original population since fewer individuals means there are fewer genotypes. By random chance that variation survived, many alles have disappeared Extreme form of genetic drift
bottleneck effect
Herpesvirus immunomodulatory molecules are transferred from infected to _____ cells in exosomes
bystander
Quiz: The basic component of a virion that is required to protect the nucleic acid genome is the: A)capsid B)envelope C)helix D)DNA E)icosahedron
capsid
Does PKR lead to cell activation or cell death?
cell death (Leads to inhibition of host translation, apoptosis)
New viruses emerging is because the ability of viruses to acquire new biological ____ in order to survive new selective ______ and adapt to new ecological niches
characteristics, pressures
The lymph nodes are the sites where the lymph and blood ____ pathways come together
circulatory
Insect vectors in viral infections Changes in ____ causes migration of these vectors and leaves people susceptible
climates
HAV released from cells is _____ in host-derived membranes, protecting the virion from antibody-mediated neutralization
cloaked
Mutant virus replicates normally in IFN-deficientVero cells but severely impaired in IFN-____ cells
competent 293T
Quasispecies diversity determines pathogenesis through _____ interactions in viral populations
cooperative
Memory B cells circulate for _____
decades
Measles virus infection in monkeys ____ preexisting immune memory
deletes
Identify which virus replication is this from the Baltimore Classification: identical to host transcribed directly from incoming viral genome to mRNA new mRNA provides critical factors for replication of dsDNA, these early genes go back and help with replication ex. Herpes and pox viruses
dsDNA virus replication
What is a key PAM that will bind to the signaling cascade to promote transcription and translation of type I interferon ?
dsRNA
Identify which virus replication is this? (Baltimore Classification): segmented virus Rio virus has 10 different RNA segments carries with it all proteins required for transcription all 10 segments simultaneously transcribed to mRNA those 10 mRNA immediately translated into protein proteins go on to make capsid (+)mRNA template for - strand
dsRNA virus replication
PKR is an interferon-induced enzyme that is activated by _____, leading to phosphorylation of ____ and inhibition of translation GDP. eIF2alpha dsRNA, eIF2alpha dsRNA, eIF2B ssRNA, eIF2alpha None of the above
dsRNA, eIF2alpha
No adaptive immune response =
early infection is controlled but no clearance of infection
What are the different techniques for direct detection? ____ = visualization of virus particles _____= visualization of virus proteins (particles or antigens) _____ = antibody detection of virus proteins (particles or antigens) _____ = molecular detection of virus nucleic acids (genome or transcripts)
electron microscopy = visualization of virus particles immunofluorescence = visualization of virus proteins (particles or antigens) ELISA = antibody detection of virus proteins (particles or antigens) PCR = molecular detection of virus nucleic acids (genome or transcripts)
Diversity of the quasispecies per se, rather than selection of individual adaptive mutations, correlates with _____
enhanced pathogenesis
Signaling via Pi3K facilitates virus ____
entry
What do SOME viruses have?
envelope - lipid membrane provided by the host
Nucleocapsid + lipid membrane, glycoproteins = _____ ______
enveloped virus
Every T cell makes a different TCR(T cell receptor) - and every TCR binds to a different _____
epitope
Plasma cells secrete antibodies that bind very specifically to particular protein sequences called _____
epitopes
Mutation is a powerful advantage, but selection and survival balances genetic fidelity and mutation rate. This limit is called the _____
error threshold
Which protein is a proofreading enzyme for covid?
exonuclease (ExoN;nsp14)
T/F: coroanaviruses bud at the plasma membrane
false
T/F: the HE spike of coronaviruses is responsible for fusion of the viral and host membranes
false
Innate immunity is also important because it ____ into adaptive immunity
feeds
•G64S mutant populations had 6-fold ____ mutations than WT populations (~0.3 mutations per genome vs. ~1.9 mutations per genome) •G64S mutant virus was not defective in replication efficiency in vivo/vitro
fewer, vitro
To examine biological role of viral quasispecies, group wanted to test the effect of enhanced RdRp fidelity. Poliovirus with a single amino acid change in RdRp, G64S, displayed increased ____
fidelity
What family is ebola a part of?
filovirus
In evolutionary biology, _____ landscapes are used to visualize the relationship between genotypes and reproductive success. It is assumed that every genotype has a well-defined replication rate (often referred to as fitness).
fitness
Quiz: The Baltimore classification system, the most commonly used virus classification system, groups viruses based on A. genome structure, plus reverse transcriptase B. genome structure C. capsid symmetry D. presence of absence of an envelope E. amino acid sequence
genome structure, plus reverse transcriptase
IFN binding to cell surface receptors induces signaling that leads to expression of ...
hundreds of interferons stimulated genes "ISGs"
What are the two configurations(shapes) of capsids?
icosahedral helical for both enveloped and naked
What cell take the virus to the lymph node?
immature DC or macrophages
When did the first serious SARS example happen?
in 2002-3 epidemic associated with 8273 confirmed cases and 775 deaths (9% mortality), in at least 37 counties
How were researchers able to create 472C from the 472U (vaccine)?
in the reverent they introduced a mutation to create a restriction site when together
Match :virus-first, or virus early hypothesis 1. increase in complex city and emergence of translation 2. Autonomous replication or selfish cellular genes 3. Reductive evolution, loss of relation and obligate parasitism
increase in complex city and emergence of translation
How is HBV infection associated with development of type 2 diabetes
infection stimulates levels of enzyme involved in glucose synthesis Interfering with metabolic pathways to benefit virus replication
Does the innate or adaptive slow down initial virus?
innate
PRR recognition of virus infection result in a signaling cascade that induces _____
interferon (IFN)
What are the genes that JAK-STAT upregulates called? What do they do?
interferon-stimulated genes or ISGs Many directly interfere with the viral replication processes (block virus replication)
What is ISRE? What do they stimulate?
interferon-stimulated response element is in the promoters of hundreds of genes Stimutate ISGs or interferon-stimulated genes and function to block specific steps in viral replication A cell expressing ISG is said to be in an anti-viral state
Where does budding occur?
into intracellular vesicles
How do you spread a virus through direct contact?
lesions saliva sex animal or insect bite maternal-neonatal
Quiz: Enveloped viruses are susceptible to many environmental stresses such as dehydrating agents due to the sensitivity of their: A. lipid membrane B. capsid C. nucleic acid genome D. nucleocapsid E. glycoproteins
lipid membrane
After iDC(immature dendritic cells) takes up antigen, it becomes activated to a ____ and can now stimulate T cell responses
mDC (Mature dendritic cell)
mDCs stimulate activation of CD8 T cells, which undergo _____ expansion and _____
mDCs stimulate activation of CD8 T cells, which undergo clonal expansion and proliferation
What do measles have cell tropism for?
macrophages, dendritic cells, T cells, B cells, epithelial and endothelial cells, neurons
How do you sequence quasispecies according to the size below(genetically)? major populations (>10% quasispecies) intermediate populations (10%-1% quasispecicies) minority populations (>1% quasispecicies)
major populations; population-based sequencing intermediate populations; clonal sequencing minority populations; Next-generation sequencing
Quiz: Naked capsid virus entry into a cell is usually via endocytosis, whereas enveloped viruses are released into the cell after undergoing A. membrane fusion B. phagocytosis C. pore formation D. macropinocytosis E. vessicle formation
membrane fusion
Key to measles dissemination is infection of _____ immune cells
migratory
How many TCRs (T cell receptors) are there?
millions
In signal transduction host cell govern how it responds to its environment and viruses ____ how that happens, they intercept into these pathways for its own benefit Activate or ____ pathways
modify, inhibit
What are some routes of entry?
mucus membrane or skin respiratory oral sexual ocular percutaneous (needles, wounds, bites)
Exosomes are 30- to 150-nm vesicles generated by inward budding on the cytoplasmic endosome-derived membranes of the ____
multivesicular bodies (MVBs)
Replicating viruses produce large numbers of ____ genomes
mutant
What is entry via percutaneous?
needles, wounds, bites
Increasing the fidelity of poliovirus replication has a negative/positive effect on viral adaptation and pathogenicity
negative
Antibodies produced by plasma cells can prevent infection by .....
neutralization, or can facilitate killing of infected cells
non enveloped virus entry via? enveloped?
non enveloped: endocytosis enveloped: membrane fusion
What do ALL viruses have?
nucleic acid capsid - protein coat encoded by the virus
IFN binding to cell surface receptors induces signaling that leads to expression ....
of hundreds of interferon stimulated genes "ISGs"
What do measles have tissue tropism for?
pantropic (lungs, lymph nodes, spleen, liver, kidney, GI tract, thymus, skin, rarely CNS)
Measles virus is a _____ that infects via the respiratory route and then disseminates to many tissues in the body
paramyxovirus
The PRR recognizes molecules that are produced by a virus that is referred to as ______ These are foreign to the cell so they act as danger singals.
pathogen-associated molecular patterns or PAMs
Viral TAP inhibitors interfere with _____ translocation
peptide
The Nidoviralesorder of ____-sense RNA viruses make nested sets of mRNAs
positive
Which two polyproteins can ORF1a and ORF1b produce? How does ORF1b get transcribed?
pp1a (shorter but more abundant) pp1ab( longer but rarer because it requires a ribosome frameshifting site)
Adenovirus VA RNA I _____ activation of PKR
prevents
What is the function of the S glycoprotein?
promotes receptor binding and fusion 20nm spikes HEAVILY glycosylated In BCoV & MHV: S cleaved to S1, S2 - remain associated
Numerous viruses can be released from infected cells in _____ form
quasi-enveloped
Genetic diversity includes mutational events but it also includes ____-
recombination
Measles Earlier studies showed _____ in innate and adaptive immune responses shortly after measles infections
reductions
Icosahedral capsid regular polygons with ___ triangular faces regular = each face is different/identical icosahedral capsids exhibit the same ___ but are not "____" polygons
regular polygons with 20 triangular faces regular = each face is identical icosahedral capsids exhibit the same SHAPE but are not "regular" polygons
What is the reservoir and intermediate of SARS?
reservoir: Bats Intermediate: civets cats
Human coronaviruses cause ____ disease of varyings severity
respiratory
Retrotransposons in host genomes share many similarities with _____
retroviruses
What is a type I interferon receptor binding to type I interferon cytokine on the same cell known as? neighboring cell?
same cell: autocrine signaling neighboring cell: paracrine signaling
What kind of viruses can do reassortment?
segmented viruses
Mutation is a powerful advantage, but _____ and ______ balances genetic fidelity and mutation rate
selection and survival
PCR is an excellent way to detect viral genomes or viral transcripts in tissue, cell, or fluid samples, but requires an educated guess for testing purposes because of the need to use A. viral antigens B. protein-specific antibodies C. sequence-specific RNA D. DNA nucleotides E. sequence-specific primers
sequence specific primers
What is this an example of? Binding of ebolavirus; bind to fusion receptor and then nucleocapsid ends up inside the cell
signal transduction
What is this an example of? Up regulate the channel in the endosome membrane that pumps protons into the endosome and drops the pH then that will uncoat the virus
signal transduction
If you were to measure infectious titers 2 hours after infection, you would most likely observe a: A. 100,000-fold increase in virus titer B. 1000-fold increase in virus titer C. significant drop in virus titer D. no change until an increase is observed E. small increase in virus titer
significant drop in virus titer
What is SUMOylation? why is it important?
similar to ubiquitination, where the host as SUMO proteins to these IRFs as part of the negative feedback regulation of the interferon response host produces interferon to block virus replication but it cant keep that indefinitely. It has a negative feedback response after a certain period of time that shuts off interferon expression once the viral infection is under control
Capsids are usually:
simple = 1-3 proteins symmetrical
Unlike mammalian cells in which information flows from DNA to mRNA to protein, some viruses have evolved enzymes called "Reverse Transcriptase" which can convert.... double stranded RNA into DNA single stranded RNA into DNA single stranded DNA into RNA double stranded DNA into mRNA
single stranded RNA into DNA
The researchers found that at high mutation rates, genotypes with a ____ replication rate can displace faster replicators if the former has a higher "____"—or fitness—against mutations; that is, if a mutation is, on average, less harmful to the slower replicator than to the faster one.
slower, robustness
What is the function of HE protein?
smaller spikes 5-7nm found on some group I and II coronaviruses, NOT SARS frequently deleted during cell passaging = non essential 65-70kD glycosylated disulfide-linked dimer Hemagglutination activity = binds sialic acid = involved in binding? Esterase activity = degrades sialic acid = involved in release of virus from cells?
What organ filters the blood?
spleen
While pathogens in the tissue are picked up in the lymphatic system, blood borne pathogens are decked by the filtration system in the _____
spleen
Identify which virus replication is this? (Baltimore Classification): not quite closed ds circle, so part is ss translated to +mRNA to proteins least efficient viruses go into capsid +RNA, RT activates, ssDNA copy of +RNA, then ds DNA copy thats mostly circular again
ss/dsDNA retrovirus replication
Identify which virus replication is this from the Baltimore Classification: _____ virus replication ssDNA has to have antisense copy host cell polymerase makes it from both copies, very similar to dsDNA replication ex. parvovirus
ssDNA virus replication
At a low mutation rate, a faster replicator would displace a robust one. However, beyond a critical mutation rate, the slower replicator should outcompete the faster replicator. This phenomenon is known as the "_____"
survival of the flattest
Effector CD8 T cells return to ....
the site of infection and kill target cells
Cytotoxic 'effector' CD8 T cells return to .....
the site of infection and kill virus infected cells - the 'virus factories'
What supports the Progressive/escaped/vagrancy hypothesis
the striking similarities between prevalent genetic elements in eukaryotic genome called retrotransposons and retroviruses
What is the virome?
the total collection of viruses in and in the human body
which of the features is shared among all coronaviruses A)They are all nonenveloped. B)They all have DNA genomes. C)They all produce a nested set of subgenomic mRNAs. D)They all infect fish.
they all produce a nested set of subgenomic mRNAs
Memory CD8 T cells remain in ....
tissue or circulate for decades
Why do viruses remodel cellular organelles?
to produce replication sites
A restricted quasispecies of poliovirus is less neuropathogenicand critical in viral tissue _____
tropism
acute respiratory distress during a SARS infection is likely caused by a cytokine storm
true
The viral mutation rate is finely ____ and has probably been optimized during evolution of the virus
tuned
Intergovernmental Panel on Climate change list ____ borne diseases among the consequences most likely to change due to global warming
vector
Measles infection leads hosts _____ to infections for which they had developed memory immunity
vulnerable
When a cell is infected with an ebola virus and has normal interferon treatment, where is STAT located? Where should it if it is infected with a normal virus ?
with ebola virus; cytoplasm nromal virus; nucelus
Describe the envelope
~80-120nm Petal-shaped spikes = S protein, give virions crown-like morphology Fringe of shorter spikes = HE
What are some examples for very different outcomes of infections? Flu: HIV: Herpes:
• FLU fast onset of disease and virus is cleared • HIV months to years before symptoms develop • Herpes infections are life-long and cannot be cleared
Examples of viral bottlenecks in nature:
• Small droplets of suspended virus during aerosol transmission • Activation of latent virus from a limited population of cells • Small volume of inoculum introduced in infection by insect bites
Covid-19 Case fatality rate
•Age-dependent, with elderly being much more vulnerable to severe and fatal infections •Overall CFR estimated at 1-3% currently, but this could be an overestimate if the rate of asymptomatic infections is high (however, very recent studies in multiple countries suggest the asymptomatic rate is not high) •South Korea has reported much lower CFR after extensive testing •Italy reporting CFR of 7.3%; likely due to lack of testing of mild cases, relatively older population, overwhelmed healthcare system
Coronavirus Disease
•Common and diverse group of viruses •Infect many types of mammals and birds •Cause respiratory, gastrointestinal, and CNS diseases •Cause 5-30% of human respiratory infections •Usually acute and self-limited disease; can lead to chronic infections •229E and OC43 prototypes are etiologic agents of the common cold •SARS first example of serious illness in humans caused by a coronavirus: 2003 epidemic associated with 8273 confirmed cases and 775 deaths (9% mortality), in at least 37 countries
What happens if you exceed the error threshold for mutation? below it?
•Exceed it: loss of infectivity •Below it: cannot produce enough mutations to survive selection
Middle East Respiratory Syndrome (MERS) Coronavirus
•Identified in Sept. 2012 in patient from Saudi Arabia that died of severe pneumonia •Retrospective study of stored samples confirmed a cluster of cases in Jordan in April, 2012 (n=11, 2 fatalities) •Clinical symptoms similar to SARS with major respiratory difficulties; diarrhea & vomiting in 25% patients •High 36% mortality rate but most have comorbidities •~2500 cases and 858 deaths in 27 countries since 2012 but all cases linked to countries in and around the Arabian peninsula •Does not appear to spread efficiently human-to-human
Word bank: close, far below •RNA viruses: evolve ___ to their error threshold •DNA viruses: evolve ____ to their error threshold
•RNA viruses: evolve close to their error threshold •DNA viruses: evolve far below to their error threshold
SARS pathogenesis
•Replicates in lung and causes alveolar damage and multi-nucleated giant cells •Major infiltration of macrophages •Thought be very efficient at evading or antagonizing type I interferon but to induce high level of proinflammatory cytokines which may be pathologic •Active replication in intestinal epithelial cells but no tissue damage here, mechanism of diarrhea unclear; can be shed in feces as well as nasal secretions •In fatal cases, evidence of systemic infection (virus detected in many tissues) •Age dependence of severity of infection observed in animal models as well
What are some of the Consequences of selection on a quasispecies?
•Viral infections are initiated by a population of particles, not a single virus particle •The large number of progeny produced are complex products of selective forces inside the host •Survival of the fittest: A rare genome with a particular mutation may survive a selection event, and this mutation will be found in all progeny genomes (e.g., drug-resistant genome)•Linked but unselected mutations can get a free ride •Consequently, the product of selection after replication is a new, diverse population that shares only the selected mutations
SARS-CoV-2
•Wide range of symptoms, from asymptomatic to severe illness -Cough-difficulty breathing-Fever-Chills-muscle pain-sore throat-nausea, vomiting, diarrhea-loss of taste and smell-Kawasaki disease in children? •Symptoms appear 2-14 d after exposure
