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Disease & Defense - Unit 3 > Host Response to Viral Infection > Flashcards

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

General outcomes of viral infection of cell

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

Cytopathic effects definition

any detectable morphologic changes in the host cell

3

Causes of direct cell damage from viral infection

-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

Types of morphological cytopathic effects and viral causes

-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

Types of inclusion bodies and viral causes

-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

Causes of indirect cell damage from viral infection

-integration of viral genome
-induction of mutations in host genome
-inflammation
-host immune response

7

Permissive vs. Nonpermissive cell definition

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

8

Innate defenses against viral infection

-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

Innate vs. Adaptive immunity against viral infection (generally)

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

10

Intracellular restriction factors and examples

-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

Important TLRs in viral infection

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

12

Class of proteins (other than TLR) that recognize viruses

-Retinoic acid-inducible gene I-like helicases (RLHs)
-coordinate similar pathways to TLR

13

Type I IFNs

-alphaIFN and betaIFN
-secreted by most infected cells w/in hours of infection
-antiviral cytokines produced transiently

14

Type II IFNs

-gammaIFN
-produced only by T cells and NK cells

15

Cell response of IFN

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

16

Characteristics of the anti-viral state

-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

Major mediators of IFN-induced anti-viral state

-PKR=protein kinase that phosphorylates (inactivates) translation initiation factor --> decreased protein synthesis
-OAS=activates ribonuclease that degrades mRNA

18

Cytokines of the innate immune system

-small proteins that help body respond to infection
-IFN, IL-1, TNFalpha, IL-6, IL-12, IL-18

19

Chemokines of innate immune system

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

20

Role of NK cells in viral infection

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

21

Humoral response to viral infection

-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

Group specific vs. type specific Abs

-group=see epitopes shared by all of a virus group
-type=see epitopes defining a virus group subset

23

Cell-mediated response to viral infection

-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

Viral strategies to evade host defense (7)

-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

Example of viruses that produce proteins to inhibit host defense

-Pox
-Herpesviruses

26

Examples of antigenic variation

-antigenic drift (point mutations)=HIV, influenza A
-antigenic shuffling=influenza A

27

Example of down-regulation of host proteins

-Pox
-Herpesviruses

28

Example of infection of immunoprivileged sites

-e.g. brain
-HSV

29

Examples of direct infection of the immune system

-HIV
-EBV

30

Examples of inhibition of apoptosis/cell cycle control

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