Host Responses to Viral Infections (complete)

Question 1

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

Answer 1

• 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

Question 2

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

Answer 2

1) Indirect cell damage

2) Direct cell damage

Question 3

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

Answer 3

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

Question 4

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

Answer 4

Morphological changes:

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

Inclusion bodies:

• Negri bodies (rabies)
• Chromatin clumps

Question 5

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

Answer 5

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

Question 6

Describe transformation as a viral effect on host cells

Answer 6

• Can promote tumor genesis

- AKA: cell growth w/o restraint

Question 7

Describe cell lysis as a viral effect on host cells

Answer 7

• Result in destruction of host cell

- Said to be more effective in viral infections

Question 8

Describe persistent infections as a viral effect on host cells

Answer 8

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

Question 9

Describe latent infections as a viral effect on host cells

Answer 9

• Show delay between infection and appearance of symptoms

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

Question 10

Describe the innate defenses as they relate to viral infections

Answer 10

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

Innate immunity: Non-specific and immediate

Question 11

What are intracellular restriction factors?

Answer 11

• 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

Question 12

Describe APOBEC

Answer 12

• Binds to viral DNA/RNA

- Mechanism is unknown

Question 13

Describe TRIM5

Answer 13

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

Question 14

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

Answer 14

INTERFERONS

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

Question 15

How does IFN stimulate a cell?

Answer 15

• 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

Question 16

What is the responsive element for Type 1 IFNs?

Answer 16

Interferon-stimulated response elements (ISREs)

Question 17

What is the responsive element for Type 2 IFNs?

Answer 17

Gamma activated site (GAS) elements

Question 18

Describe the anti-viral state induced by interferons

Answer 18

• 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

Question 19

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

Answer 19

1) PKR

2) OAS

Question 20

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

Answer 20

• Protein kinase

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

Question 21

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

Answer 21

• 2’-5’ oligoadenylate synthetase

- Activates a cellular ribonuclease (RNAseL) that DEGRADES mRNA

Question 22

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

Answer 22

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

Question 23

What does TLR 3 respond to?

Answer 23

dsRNA

Question 24

What does TLR 7 respond to?

Answer 24

viral RNAs

synthetic ligands

Question 25

What does TLR 9 respond to?

Answer 25

unmethylated CpG

Question 26

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

Answer 26

- 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)

Question 27

What are the different virus strategies to evade host defenses?

Answer 27

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

Question 28

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

Answer 28

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

Question 29

Describe the cell-mediated response to virus infections

Answer 29

- 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