Ebola

Question 1

Ebolavirus characteristics

Answer 1

filovirus

enveloped

negative ssRNA

glycoprotien is only viral protein on the surfaced - binding and entry

Question 2

Ebola genome

Answer 2

neg ss virus

7 genes, 8 proteins (2 forms of glycoproteins - one is shed and one is anchroed -distract immune systen

Question 3

EBV ecology

Answer 3

fruit bats = resivoir - PCR +, no virus

transmission to humans through contaminated fruits - primates (monkey meat)

Question 4

EBV lifecycle

Answer 4

1. large virus - enters by macropinocytosis (doesn’t trigger immune)
2. endsoome -lysosome - acidification!
3. fusion of viral envelope w endosome membrane (acidic + NPC1)
4. negative strand –> positive strand make a lot more RNA
5. also, negative strand transcribed to positive strand and translated and processed
6. new viral proteins bud off

Question 5

VP35

Answer 5

blocks IFN induction

RIG-I rec virus and stim IFN, VP35 blocks signal

also blocks RNAi

Question 6

VP24

Answer 6

blocks IFN action

in cell that IFN is signaling

if virus infects cell, makes VP24 so any IFN that comes there can’t have effect

inhibits nuclear translocation of STAT 1/2, binds to karyopherin (TF for ISGs)

Question 7

karyopherin

Answer 7

ferries STAT complex across nuclear membrane, VP24 blocks binding site so STAT proteins can’t make ISGs

Question 8

VP35

Answer 8

blocks dendritic cell maturation –> poor t cell maturation

inhibits maturation so can’t process and present on MHC well

slows adaptive response

Question 9

tetherin

Answer 9

induced by Type I IFN - blocks viral budding and cell-cell spread, leads to endocytosis of ebola and degredation

EBOV glycoprotein binds tetharin and rprevents it from working!

Question 10

Brincidofovir

Answer 10

DNA pol inhibitor

not FDA approved

didn’t make sense (RNA)

didn’t work

Question 11

RNAi

Answer 11

normal event manipulated

give siRNA into cells - make dsRNA

RISC complex separates strands - complimentary strand with viral RNA - makes dsRNA - cleavage

had mutated - promising but don’t know if it works

Question 12

How do survivors survive without treatment?

Answer 12

adaptive immunity allows recover from infections that subvery innate immunity

rapid increase in IgG and IgM - adaptive response

Question 13

ZMapp

Answer 13

antibody treatment

3 mAbs against EBOV glycoprotein - partially humanized murine abs made in tobacco plants

kept alive but decreased supply

give survivor serum

Question 14

ChAD (Z) vaccine

Answer 14

ChAD (Z)

CD8+ T cell immunity!

immunity to adenovirus vector (have a lot of abs)

short lived immunity but can be boosted

recombinant, nonreplicating vector - engineered to express ebola glycoprotein

Question 15

recombinant VSV-Ebola vaccine

Answer 15

ebola glycoprotein gene used to relace glycoprotein of VSV (vesicluar stomatitis virus)

ring strategy

limited relication after administration

protects nonhman primates after a simgle dose

induces antibodies

inhibited by t cell depletion before but not after

after supposed to have immunity - no one got ebola!!