Viral Pathogenesis Intro and Adeno Flashcards

1
Q

Host detection of viral RNA

A
  • cytoplasmic and endosomal RNA sensors
  • dsRNA/ssRNA sensors include PKR, RIGI, MDA5
  • endosomal receptors are TLR3/7
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2
Q

Virus Disease (2 factors)

A
  1. direct effects of virus on cells, tissues, organs

2. Indirect effects (immune mediated)-host response can be harmful

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3
Q

Host Detection of viral RNA and IFN induction

A
  • interaction of RNA w/ RNA sensors activates TFs (IRF3, NF-kappaB)
  • TFs induce Tc of type 1 IFNs
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4
Q

Host Cell Detection of viral RNA through PKR and translational inhibition (dsRNA)

A
  • dsRNA activates PKR
  • PKR undergoes autophosphorylation, dimerizes and phosphorylates eIF2alpha
  • phosphorylated eIF2alpha binds eIF2B
  • inhibition of translation initiation

-dsRNA activation of 2’5 oligo adenylate synthase
-enzyme produces a chain of adenines linked 2’5
causes dimerization of RNase L, chews up RNA in cell

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5
Q

Host Detection of viral DNA

A
  • if DNA is replicating in cyto will be recognized as foreign-DNA is only in nucleus
  • pox are large DNA viruses, lots of machinery needed for rep, rep in cyto
  • DNA recognized by cGAS, which produces cGAMP
  • activates IRFs and NF-kappaB
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6
Q

Viral Defense against host defense

A

-blocking innate response

Viral homologues of

  • Fc receptors
  • IFN alpha, gamma, beta
  • TNF receptors
  • cytokines
  • MHCI-secreted and compete for binding
  • complement interference
  • interference of Ag presentation by MHCI
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7
Q

Viral Blockers of Ag presentation by MHC1

A

HIV tat, adeno E1A block MHC gene Tc
hCMV US11, US2 enhance proteososme degradation of MHC
HSV ICP47, EBV EBNA interferes w/ TAP

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8
Q

Adeno E3 19K protein (4)

A
  • retains class I MHC molecules in ER blocking presentation of antigenic peptides to CD8 T cells
  • membrane glycoprotein expressed by all Ad serotypes (except A and F)
  • N terminal lumenal domain assoc. w/ lumenal domain of MHC1 molecules
  • C terminal cytosolic tail block transport of MHCI molecules to cell surface through ER retention motif
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9
Q

Adeno E3 14.7 K protein (4)

A
  • inhibits TNF alpha mediated cytotoxicity
  • blocks ligand induced TNFR1 internalization, preventing DISC formation
  • inhibits recruitment of FADD, TRADD, caspase 8 to death domain
  • E3 promoter also contains NF-kappaB binding site, which is activated by TNF alpha
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10
Q

Adeno E3 10.4 K and 14.5 K proteins

A

E3-10.4K (RID alpha) and 14.5 K (RID beta) proteins assoc. to form receptor internalization complex (RID)

  • accelerates clearance of Fas and TRAIL receptors from cell surface
  • inhibits inflammation and apoptosis
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11
Q

VA RNAs

A
  • act as dsRNA decoys bind and inactivate PKR
  • may also act as miRNAs to modulate host gene expression
  • the complex secondary structure of VA interferes w/ the rxn, stopping phosphorylation and dimerization
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12
Q

EIA region

A
  • drive cells into S phase to favour vrep
  • inhibits MHCI Tc
  • causes redistribution of histone acetyltransferases which regulate Tc (p300/CBP)
  • inhibits p53 mediated Tc activation
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