Host Responses to Viral Infections (complete) Flashcards
What is something to keep in mind about host response to viral infections?
- 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
What are the two ways to measure cytopathic effects of virus infection?
1) Indirect cell damage
2) Direct cell damage
What is indirect cell damage in response to a virus infection?
- Integration of viral genome
- Induction of mutations into host genome
- Inflammation
- Host immune response
What are some examples of direct cell damage as a result of virus infection?
Morphological changes:
- Cell lysis
- Nuclear shrinking
- Cell fusion
- Membrane alterations
Inclusion bodies:
- Negri bodies (rabies)
- Chromatin clumps
What are the effects that viruses have on the cells they infect?
1) Transformation
2) Cell Lysis
3) Persistent infections
4) Latent infection
Describe transformation as a viral effect on host cells
- Can promote tumor genesis
- AKA: cell growth w/o restraint
Describe cell lysis as a viral effect on host cells
- Result in destruction of host cell
- Said to be more effective in viral infections
Describe persistent infections as a viral effect on host cells
- Viruses are produced and reproduced w/in the cell
- But there is NO cell lysis
- Can occur over long periods of time
Describe latent infections as a viral effect on host cells
- Show delay between infection and appearance of symptoms
- Have capacity to produce/reproduce viruses, but don’t do so like persistent infections
Describe the innate defenses as they relate to viral infections
- Natural barriers
- Specific cells (macros, PMNs)
- Soluble factors (IFN, cytokines, complement)
Innate immunity: Non-specific and immediate
What are intracellular restriction factors?
- 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
Describe APOBEC
- Binds to viral DNA/RNA
- Mechanism is unknown
Describe TRIM5
- Abundant
- Bind to specific capsid structures/folds
- Can interact w/ Fc structures
- Can prevent disassembly of capsid coat
What is the most important way that the host restricts virus infection? Explain
INTERFERONS
- The neighboring cell is not affected if IFN is released from host cell
- Type 1 and Type 2 (very distinct!)
How does IFN stimulate a cell?
- 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
What is the responsive element for Type 1 IFNs?
Interferon-stimulated response elements (ISREs)
What is the responsive element for Type 2 IFNs?
Gamma activated site (GAS) elements
Describe the anti-viral state induced by interferons
- 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
What are two important mediators of the IFN-induced anti-viral state?
1) PKR
2) OAS
Describe PKR as a mediator of the IFN-induced anti-viral state
- Protein kinase
- Phosphorylates and inactivates cellular translation initiation factor => DECREASED protein synthesis
Describe OAS as a mediator of the IFN-induced anti-viral state
- 2’-5’ oligoadenylate synthetase
- Activates a cellular ribonuclease (RNAseL) that DEGRADES mRNA
What are 3 important toll-like receptors needed for innate responses to virus infections?
1) TLR 3
2) TLR 7
3) TLR 9
What does TLR 3 respond to?
dsRNA
What does TLR 7 respond to?
viral RNAs
synthetic ligands
What does TLR 9 respond to?
unmethylated CpG
What types of Abs are used in a humoral response to viruses?
- 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)
What are the different virus strategies to evade host defenses?
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
What are the ways viruses can interfere with the IFN system?
1) Block IFN synthesis
2) IFN R decoys
3) Block IFN signaling
4) Block IFN induced transcription
5) Block IFN induced protein functions
Describe the cell-mediated response to virus infections
- 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
