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Fundamentals I > RNA viruses > Flashcards

RNA viruses Flashcards

1
Q

Factors that decide a virus’s tissue tropism

A

1) Cell receptors
2) Proper expression of transcription factors and replication co-factors that recognize viral promoters and enchancer sequences
3) Ability of cells to support viral protein synthesis
4) Presence or absence of physical barriers, including pH, temp, O2 tension…

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2
Q

Sequence of Viral Spread

A

1) Implantation at portal of entry
2) Local replication and local spread
3) Dissemination from portal of entry
4) Multiplication in target organ
5) Shedding of virus

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3
Q

At what point in viral spread do you usually see clinical disease?

A

multiplication in the target organ

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4
Q

What is incubation period?

A

Time between exposure to the virus and onset of disease: extends from implantation until virus replicates in target organ causing symptoms

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5
Q

What is pathogenesis?

A

Process by which an infection leads to disease. Results from viral disruption of normal cellular processes.

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6
Q

Name basic pathogenesis for following viruses:
HIV
Hep C
Poliovirus

A

HIV: immunosuppression and syncytia formation
Hep C: liver dysfunction, primarily as a response to host defenses
Poliovirus: Host “shut-off” phenomenon
-also applies to vesicular stomatitis virus, encephalomyocarditis, influenza

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7
Q

What is host shut-off phenomenon

A

Some viruses induce a shutoff of all host cellular protein synthesis with a shift to viral protein synthesis.

Severe stress for cell:culminates in lysis and tissue destruction

ex: rhinovirus, polio, influenza

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8
Q

Positives and negatives of viral induced apoptosis (with nuclear inclusions)

A

Positive: small scale apoptosis blocks viral replication and spread

Negative: Systemic apoptosis leads to massive tissue destruction with sever pathogenesis

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9
Q

Processes of viral infection that trigger disease, with examples

A

1) Toxic effects of viral gene products on cell metabolism (host shutoff)
2) Host response to infected cells (liver damage from Hep C, syncytia formation from HIV)
3) Modification of cellular function due to interaction of cellular genes and proteins with viral products (oncogenic viruses)
4) Lytic destruction of host cells (acute viral infections)

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10
Q

What is the difference between mutation and recombination?

A

Mutation: error is incorporated into the viral genome

Recombination: coinfecting viruses exchange genetic information creating novel virus

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11
Q

What is mutation rate for DNA viruses?

A

Approximates rate for eukaryotic cells: 10^-11 errors per nucleotide per round of replication

Due to proofreading polymerases

Only one mutant per several hundres-thousands of genome copies

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12
Q

What is antigenic drift?

A

mutations that produce viruses with new antigenic determinants that can cause disease in previously resistant host

AKA quasispeciation

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13
Q

What is the key criteria for viral recombination?

A

Co-infection of a single cell with two or more viruses. Can be different strains or different types of virus.

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14
Q

What are the 3 types of Viral Recombination?

A

Independent reassortment
Homologous recombination
Breakage/re-joining

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15
Q

Key features of independent reassortment

A

Viruses must have segmented genomes

Process involves genes residing in different pieces of nucleic acid being randomly assorted

Results in generation of a virus with new antigenic determinants and new host ranges: Antigenic shift –> major cause of epidemics such as 1918 influenza

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16
Q

Key features of homologous recombination

A

Occurs by template switching during RNA replication

  • Must have homology for direction switching
  • Common in RNA viruses and retroviruses
  • requires NO breaks!

ex: multi-drug resistant HIV
Every HIV genome produced is likely a product of ~8 of these “template switching” recombinations

17
Q

Key features of breakage/re-joining

A

Requires nucleic acid break or fragmentation
Fragments are ligated: only viruses still able to replicate survive
Co-infecting viruses must have similar genomes
Prevalent among DNA viruses; occurs in large RNA viruses

ex: generation of SARS coronavirus

18
Q

Major Bio features of Orthomyxoviruses

A

Prototype: Influenza

Enveloped, segmented, negative-stranded (remember: influenza is non-sense!)
Lipid bilayer with hemagglutinin and neuraminidase spikes
Carries RNA-dependent RNA polymerase
Type specificity common internal antigens NP and M1
Subtype specificity envelope antigens hemagglutinin (HA) and neuraminidase (NA)

19
Q

2 mechanisms by which influenza alters its antigenic constitution

A

By altering antigenic constitution, influenza delays clearance by the immune system

Antigenic Drift: gradual accumulation of minor mutation –> seasonal flu differences

Antigenic Shift: sudden, major change in the antigenicity of a virus due to recombination of the virus genome with another genome of a different antigenic type
-immune system fails to recognize new antigenic type –>epidemic and pandemic strains

20
Q

Transcapsidation:

A

lab technique where cell is infected with 2 different viruses and the genome of one is inserted into protein structure of another

ex: generation of viral vectors for gene therapy

21
Q

Main features of HCV virus

A

Flavivirus: + ssRNA; enveloped

22
Q

Main features of SARS

A

Coronavirus: +ssRNA; enveloped

23
Q

Major features of influenza

A

Orthomyxovirus

Carries out independent reassortment: ex 2009 H1N1 had 4 distinct recombination events

Enveloped, segmented, negative-stranded
Lipid bilayer with hemagglutinin and neuraminidase spikes
Carries RNA-dependent RNA polymerase
Type specificity common internal antigens NP and M1
Subtype specificity envelope antigens hemagglutinin (HA) and neuraminidase (NA)

Course of infection:
inhaled
proliferate in epithelial cells of upper respiratory tract
disseminates to target: lower respiratory tract

24
Q

What is viremia?

A

Virus in the blood (Spread through the circulation). Virus enters organs from capillaries by multiplying in endothelial cells or fixed macrophages, diffusing through gaps, carried by migrating leukocytes.

Basis for many diagnostic tests

25
Q

4 Major methods of viral dissemination

A

1) Viremia
2) Nerve cells (rabies)
3) Cell trafficking
4) Direct cell-to-cell (syncytia - HIV)

26
Q

Distinct histological feature of cells infected with CMV

A

Cells devotes lots of energy to making dark, black inclusion bodies –> eventual apoptosis

27
Q

4 Mechanisms of Viral Diversity

A

1) Mutation
2) Recombination/reassortment
3) Replication rate/number of progeny (polio: 1 - 10,000 virions in a single day)
4) Selective Pressure

28
Q

What is an escape variant?

A

Viral strain that has acquired mutations that allow it to evade immune responses or resist certain drugs

Problematic for antiviral and vaccine development

29
Q

Best method for battling extreme viral diversity and resistance due to rapid mutation

A

ex- HIV: Mutants resistant to every combination of drug (current and future) arise thousands of times everyday,
just by chance

Treat with drug cocktails, never miss doses, keep developing new drugs

30
Q

Major Features of Hepatitis C virus

A

Flaviviridae family: + ssRNA ; enveloped

Causes chronic infection in 80% of people
Major cause of liver damage world wide (200 M infected)

Error prone replication, so many quasispecies variants –> limitation to antiviral therapy, immune function and vaccine strategies

31
Q

What does recombination do that point mutations do not?

A

1) Juxtapose combinations of mutations that would have a low probability of occurring all at once (multi-drug resistance)
2) Juxtapose viral genomes with limited homology (intertypic recombination) (attenuated polio virus regaining virulence from enterovirus in Guatemala)
3) Transduce sequences from nonhomologous genomes (low frequency) (recombine with host genes: can be oncogenic!)

32
Q

What is an emerging virus?

A

A newly discovered virus or a virus that is increasing/has the potential to increase in incidence

33
Q

What are the major contributors to viral emergence?

A

High mutation rates
Recombination
Human-made changes to environment: dams, air travel, xenotransplant, urbanization, daycares…

34
Q

Key features of West Nile Virus

A

Flavivirus (same family as Hep C): + ssRNA ; enveloped

80% of infections are asymptomatic

35
Q

Picornaviruses

A

+ssRNA; non-enveloped

polio
Hepatitis A

36
Q

Reovirus

A

medium-sized, nonenveloped, icosahedryl

linear dsRNA, segmented

Readily reassorted

ex: rotavirus: kills 1M children in developing countries each year

37
Q

Key features of Paramyxoviruses and examples

A

ssRNA, negative sense; enveloped; NON-segmented

Measles
Mumps
parainfluenza
Respiratory syncytial virus (RSV)

38
Q

3 determinants of viral pathogenesis.

A
  1. Accessibility of virus to the tissue.
  2. Virus susceptibility to host defenses.
  3. Cell permissiveness to viral multiplication.

Fundamentals I (4 decks)

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