Exam 1 GMS 7133

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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


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