Marchant-15: Immune Response to Viral Infection I

Question 1

What are the 2 pathways stimulated by IFN to stimulate antiviral state?

Answer 1

• oligoadenylate synthetase (OAS1)

- Protein kinase R (PKR)

Question 2

What upregulates OAS1?

Answer 2

IFN

Question 3

What activates/alerts OAS1 activation?

Answer 3

dsRNA

Question 4

Function of OAS1

Answer 4

polymerizes ATP into 2’-5’ ATP oligomers

Question 5

Where does 2’-5’ ATP oligomers bind?

Answer 5

endoribonuclease L

Question 6

What does the OAS1 pathway accomplish?

Answer 6

degradation of ssRNA (viral and cellular)

Question 7

Where is PKR normally found?

Answer 7

cytoplasm

Question 8

What upregulates PKR?

Answer 8

IFN

Question 9

What activates PKR?

Answer 9

dsRNA

Question 10

Goal of PKR

Answer 10

block viral and cellular protein translation

Question 11

What does PKR phosphorylate to inhibit protein translation?

Answer 11

eIF-2

Question 12

What does adenovirus use to inhibit PKR action?

Answer 12

VA-RNA1

Question 13

How does VA-RNA1 inhibit PKR?

Answer 13

binds to PKR

Question 14

What do poxviruses produce to inhibit IFN action?

Answer 14

M-T7

Question 15

Function of MT7

Answer 15

• homologous to IFN receptor

- binds to cellular IFN receptor and prevents interaction with cell receptor

Question 16

What does vaccinia produce to inhibit PKR? This has a RNA binding domain.

Answer 16

E3L

Question 17

What does vaccinia produce that inhibits PKR and has homology to elF-2?

Answer 17

K3L

Question 18

Function of K3L

Answer 18

has homology to elF-2 which prevents it from phosphorylating = blocks its action and allows translation of proteins

Question 19

Function of calnexin

Answer 19

chaperone that helps MHC I alpha and beta-2-M chains assemble in ER

Question 20

What does adenovirus express that aids in localization of virus to ER?

Answer 20

E3-19K

Question 21

How is adenovirus retained in ER?

Answer 21

it has ER retention sequence (Lys-rich)

Question 22

What is the function of E3-19K?

Answer 22

binds MHC I heavy chain –> inhibits expression of MHC I on cell surface

Question 23

What does herpes virus produce to inhibit MHC I expression on cell surface?

Answer 23

ICP47

Question 24

What is the function of ICP47?

Answer 24

blocks transport of peptides into ER

Question 25

What does HCMV produce that inhibits MHC I expression at cell surface?

Answer 25

- US6-ER - Us3 - Us11 and Us2

Question 26

How does US6-ER work?

Answer 26

prevents peptides from entering ER

Question 27

How does Us3 work?

Answer 27

retains MHC in ER

Question 28

How does Us11 work?

Answer 28

translocate MHC I to cytoplasm where it degrades

Question 29

2 mechanisms of CD8 T cells in killing virus infected cells

Answer 29

- release of cytotoxic granules to target cell | - ligates Fas ligands on virus infected cell --> apoptosis

Question 30

Fas and what other ligand are signals for apoptosis?

Answer 30

TNFR1

Question 31

3 virus mechanisms to inhibit Fas and TNF killing?

Answer 31

- Caspase 8 inhibitors - DED - Downregulation of Fas receptors from cell surface