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Flashcards in Host Response to Viral Infection Deck (30)
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1
Q

General outcomes of viral infection of cell

A
  1. abortive infection (failed infection)
  2. lytic infection: production of virus and death of cell
  3. persistent infection:
    a. chronic=production of virus
    b. latent=no virus produced
    c. transforming=may produce virus
2
Q

Cytopathic effects definition

A

any detectable morphologic changes in the host cell

3
Q

Causes of direct cell damage from viral infection

A
  • diversion of cell energy
  • shutdown of macromolecular synthesis
  • occupation of ribosomes by viral mRNA
  • viral promoters and enhancers competing for cellular factors
  • inhibition of interferon defense mechanism
4
Q

Types of morphological cytopathic effects and viral causes

A
  • nuclear shrinkage and membrane proliferation (picornavirus)
  • nuclear membrane proliferation (alphavirus, herpesvirus)
  • cytoplasmic vacuolization (papovavirus)
  • cell fusion (“syncytia”) (paramyxo, coronavirus)
  • chromosomal margination/breakage (herpesvirus)
  • round and detachment of tissue culture cells (herpesvirus)
5
Q

Types of inclusion bodies and viral causes

A
  • virions and proteins in nucleus (adenovirus)
  • protein and RNA and cytoplasm=”negri bodies” (rabies virus
  • virus protein complexes and nascent virus in cytoplasm (poxvirus)
  • chromatin clumps in nucleus (herpesvirus)
6
Q

Causes of indirect cell damage from viral infection

A
  • integration of viral genome
  • induction of mutations in host genome
  • inflammation
  • host immune response
7
Q

Permissive vs. Nonpermissive cell definition

A
  • contains the machinery and components required for completion of viral replication
  • non-permissive does not
  • range of permissibilities between the two
8
Q

Innate defenses against viral infection

A
  • natural barriers: skin, mucus, ciliated epithelium, gastric acid, tears, bile
  • cells: macrophages, neutrophils, dendritic cells, NK cells
  • soluble factors, interferons, cytokines, complement, chemokines
  • intracellular restriction factors
9
Q

Innate vs. Adaptive immunity against viral infection (generally)

A
  • innate is non-specific and immediate
  • innate primes and initiates adaptive immune response
  • adaptive generally responsible for immunologic memory
10
Q

Intracellular restriction factors and examples

A
  • cellular proteins that block post-entry steps of viral infections
  • not adaptive immune response, but specific for viruses
  • viruses have evolved mechanisms to avoid restriction factors
  • e.g. Trim5 blocks retroviruses, APOBEC blocks HIV and HCV
11
Q

Important TLRs in viral infection

A

-TLR3 –< dsRNA (viruses)
-TLR4 –< fusion/envelope protein (respiratory syncytial virus)
TLR7/8 –> Imidazoquinolone (synthetic) & ssRNA (viruses)
-TLR9 –< CpG-containing DNA (bacteria and viruses)

12
Q

Class of proteins (other than TLR) that recognize viruses

A
  • Retinoic acid-inducible gene I-like helicases (RLHs)

- coordinate similar pathways to TLR

13
Q

Type I IFNs

A
  • alphaIFN and betaIFN
  • secreted by most infected cells w/in hours of infection
  • antiviral cytokines produced transiently
14
Q

Type II IFNs

A
  • gammaIFN

- produced only by T cells and NK cells

15
Q

Cell response of IFN

A
  • IFN receptors –> Jak/Stat pathways
  • control trxn of genes via:
  • ISREs (Interferon-stimulated response elements) <– Type II IFN
16
Q

Characteristics of the anti-viral state

A
  • induced by IFN binding to receptor
  • optimal state to block viral replication
  • alter trxn of 100+ genes
  • facilitated by dsRNA (intermediate in replication of some viruses)
  • blocks cell proliferation, decreases cell metabolism
  • increases antigen presentation, potentiates NK cell activity –> apoptosis
  • IFN production –> “flu-like” syndrome
17
Q

Major mediators of IFN-induced anti-viral state

A
  • PKR=protein kinase that phosphorylates (inactivates) translation initiation factor –> decreased protein synthesis
  • OAS=activates ribonuclease that degrades mRNA
18
Q

Cytokines of the innate immune system

A
  • small proteins that help body respond to infection

- IFN, IL-1, TNFalpha, IL-6, IL-12, IL-18

19
Q

Chemokines of innate immune system

A
  • chemoattractant cytokines for leukocytesm monocytes, neutrophils, and other effectors to site of infection
  • IL-8, IP10, M1P1alpha
20
Q

Role of NK cells in viral infection

A
  • activated in response to interferons or macrophage-derived cytokines
  • contain virus while the adaptive immune response generates CTL to clear infection
21
Q

Humoral response to viral infection

A
  • B cells bind viral antigen and are stimulated to divide –> plasma cells secrete Ab
  • Abs produced during primary viral infection are usually lower affinity than those produced later, and are often IgM
  • IgA: inhibits virion attachment, neutralizes toxins
  • IgG: inhibits fusion of enveloped viruses
  • IgG/IgM: opsonize or complement lysis virions
  • IgM: agglutinate virions
22
Q

Group specific vs. type specific Abs

A
  • group=see epitopes shared by all of a virus group

- type=see epitopes defining a virus group subset

23
Q

Cell-mediated response to viral infection

A
  • used to target virus by killing infected cells
  • T cells bind viral epitopes presented on MHC class I (CTL) or MHC class II (Th)
  • T cells/NK cells secrete gammaIFN
  • CTLs lyse virus-infected cells
24
Q

Viral strategies to evade host defense (7)

A
  • antigenic variation
  • immune tolerance=molecular mimicry
  • restricted expression of viral genes=”going invisible” i.e. latent infections
  • viral mlx act as inhibitors or decoys=blind or block cellular mediators or mimic
  • down-regulation of host proteins=e.g. MHC class I or adhesion mlx
  • infection of immunoprivileged sites
  • direct infection of immune system
  • inhibition of apoptosis and cell cycle control
25
Q

Example of viruses that produce proteins to inhibit host defense

A
  • Pox

- Herpesviruses

26
Q

Examples of antigenic variation

A
  • antigenic drift (point mutations)=HIV, influenza A

- antigenic shuffling=influenza A

27
Q

Example of down-regulation of host proteins

A
  • Pox

- Herpesviruses

28
Q

Example of infection of immunoprivileged sites

A
  • e.g. brain

- HSV

29
Q

Examples of direct infection of the immune system

A
  • HIV

- EBV

30
Q

Examples of inhibition of apoptosis/cell cycle control

A
  • SV40 large T antigen
  • Adenovirus E1A
  • pathway is also involved in tumorigenesis