Host Responses to Viral Infections (complete) Flashcards

1
Q

What is something to keep in mind about host response to viral infections?

A
  • We cannot generally see viral infection b/c viruses are obligate intracellular parasites
  • We do see the EFFECTS of viral infection and replication on infected cells and tissues
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2
Q

What are the two ways to measure cytopathic effects of virus infection?

A

1) Indirect cell damage

2) Direct cell damage

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3
Q

What is indirect cell damage in response to a virus infection?

A
  • Integration of viral genome
  • Induction of mutations into host genome
  • Inflammation
  • Host immune response
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4
Q

What are some examples of direct cell damage as a result of virus infection?

A

Morphological changes:

  • Cell lysis
  • Nuclear shrinking
  • Cell fusion
  • Membrane alterations

Inclusion bodies:

  • Negri bodies (rabies)
  • Chromatin clumps
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5
Q

What are the effects that viruses have on the cells they infect?

A

1) Transformation
2) Cell Lysis
3) Persistent infections
4) Latent infection

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6
Q

Describe transformation as a viral effect on host cells

A
  • Can promote tumor genesis

- AKA: cell growth w/o restraint

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7
Q

Describe cell lysis as a viral effect on host cells

A
  • Result in destruction of host cell

- Said to be more effective in viral infections

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8
Q

Describe persistent infections as a viral effect on host cells

A
  • Viruses are produced and reproduced w/in the cell
  • But there is NO cell lysis
  • Can occur over long periods of time
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9
Q

Describe latent infections as a viral effect on host cells

A
  • Show delay between infection and appearance of symptoms

- Have capacity to produce/reproduce viruses, but don’t do so like persistent infections

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10
Q

Describe the innate defenses as they relate to viral infections

A
  • Natural barriers
  • Specific cells (macros, PMNs)
  • Soluble factors (IFN, cytokines, complement)

Innate immunity: Non-specific and immediate

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11
Q

What are intracellular restriction factors?

A
  • Block/inhibit virus infection after virus entry into cells
  • Sometimes determines whether a cell is permissive or non-permissive
  • Discriminate against specific families of viruses

EXs: APOBEC, TRIM5

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12
Q

Describe APOBEC

A
  • Binds to viral DNA/RNA

- Mechanism is unknown

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13
Q

Describe TRIM5

A
  • Abundant
  • Bind to specific capsid structures/folds
  • Can interact w/ Fc structures
  • Can prevent disassembly of capsid coat
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14
Q

What is the most important way that the host restricts virus infection? Explain

A

INTERFERONS

  • The neighboring cell is not affected if IFN is released from host cell
  • Type 1 and Type 2 (very distinct!)
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15
Q

How does IFN stimulate a cell?

A
  • IFN binds to a receptor
  • Receptor activates Jak/Stat signaling
  • Have response elements specific to Type 1 and Type 2 that cause them to produce interferons
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16
Q

What is the responsive element for Type 1 IFNs?

A

Interferon-stimulated response elements (ISREs)

17
Q

What is the responsive element for Type 2 IFNs?

A

Gamma activated site (GAS) elements

18
Q

Describe the anti-viral state induced by interferons

A
  • Characteristic of a cell that has bound and responded to IFN — responding cell not infected!
  • IFN alters transcription of >100 cellular genes
  • This is the optimal state to block viral replication
  • IFN response may be triggered/activated by dsRNA

OVERALL: IFN binds to specific receptors => induces gene transcription

19
Q

What are two important mediators of the IFN-induced anti-viral state?

A

1) PKR

2) OAS

20
Q

Describe PKR as a mediator of the IFN-induced anti-viral state

A
  • Protein kinase

- Phosphorylates and inactivates cellular translation initiation factor => DECREASED protein synthesis

21
Q

Describe OAS as a mediator of the IFN-induced anti-viral state

A
  • 2’-5’ oligoadenylate synthetase

- Activates a cellular ribonuclease (RNAseL) that DEGRADES mRNA

22
Q

What are 3 important toll-like receptors needed for innate responses to virus infections?

A

1) TLR 3
2) TLR 7
3) TLR 9

23
Q

What does TLR 3 respond to?

A

dsRNA

24
Q

What does TLR 7 respond to?

A

viral RNAs

synthetic ligands

25
Q

What does TLR 9 respond to?

A

unmethylated CpG

26
Q

What types of Abs are used in a humoral response to viruses?

A
  • Group specific (bind to epitopes shared by all of a virus group)
  • Type specific (bind epitopes defining a virus group subset)
  • Neutralizing Ab (interfere w/ binding/fusion — critical for preventing re-infection)
27
Q

What are the different virus strategies to evade host defenses?

A

1) Antigenic variation
2) IFN pathway inhibition
3) Apoptosis inhibition/cell cycle control
4) Immune tolerance
5) Immunoprivileged sites
6) Immune system infection
7) Restricted expression of viral genes
8) Viral molecules that act as inhibitors/decoys
9) Down-reg of host proteins

28
Q

What are the ways viruses can interfere with the IFN system?

A

1) Block IFN synthesis
2) IFN R decoys
3) Block IFN signaling
4) Block IFN induced transcription
5) Block IFN induced protein functions

29
Q

Describe the cell-mediated response to virus infections

A
  • When virus is inside cells, Abs can’t get them
  • Now only eliminated by destruction of infected cells (function of CTK cells w/ CD8)
  • Eliminating infected cells w/o healthy tissue destruction requires CTK to be powerful and accurately targeted