Recognising virus replication

Question 1

What are cytokines?

Answer 1

A group of low molecular weight, extracellular polypeptides expressed by different immune cells - promote & regulate immune response

Question 2

What are the types of cytokines?

Answer 2

• IFNs
• Chemokines
• Interleukins
• Tumour necrosis factors
• Transforming growth factors

Question 3

What are Interferons (IFNs)?

Answer 3

Antiviral proteins that communicate to immune and non-immune cells

Question 4

What triggers release of IFNs?

Answer 4

Detection of virus by professional immune cells or infected cells

Question 5

What cells can secrete IFN?

Answer 5

all nucleated cells

Dendritic cells especially

Question 6

Who discovered IFNs?

Answer 6

Isaacs and Lindenmann - infected fibroblasts with heat inactivated influenza

Question 7

What do IFNs induce?

Answer 7

• ISGs
• MHC I expression
• activation of adaptive immune response
• NK cell activation
• T cell activation

Question 8

What are PAMPs?

Answer 8

pathogen associated molecular patterns

• unique to microbe
• not produced by host
• essential for microbial survival - cannot be changed or removed

Question 9

How are PAMPs recognised?

Answer 9

PRR - pattern recognition receptors

Question 10

What can virus PAMPs be?

Answer 10

• viral genomes

e. g. dsRNA, ssDNA

Question 11

What are the APCs that detect viral nucleic acids?

Answer 11

macrophage
dendritic cell
B cell

Question 12

What are toll-like receptors?

Answer 12

• 10 in humans
• have LRR
• TIR domain

induce pro-inflammatory response

mediate response to PAMPs

Question 13

What are the nucleic acid sensing TLRs?

Answer 13

TLR3 - dsRNA
TLR7 - ssRNA
TLR8
TLR9 - CpG nucleotides - DNA that is hypomethylated

Question 14

Where are TLR expressed?

Answer 14

NOT widely

restricted expression profile

Question 15

What is RIG-I?

Answer 15

intracellular PRR
2 CARD domains
carboxyl terminal helicase domain

crucial for RNA virus detection

Question 16

What happens if you don’t have RIG-I?

Answer 16

lose expression of ISGs (interferon stimulated genes)

Question 17

What is Influenza A virus?

Answer 17

• 100nm spheres

- 13kb genome - 8 segments

Question 18

How is influenza A virus synthesised?

Answer 18

5’ end ppp
primed with capped 10-13nt RNA fragments from cellular mRNA

copies internal U7 tract

add 150 A residues to 3’end

copied into full length antigenome

Question 19

what is the physiological ligand for RIG-I?

Answer 19

immunostimulatory RNA - 5’-triphosphate RNA

Question 20

How does RIG-I bind to 5’ ppp elements?

Answer 20

through C-terminal domain (CTD)

Question 21

How is 5’ppp RNA distinguished from host mRNA?

Answer 21

cellular mRNA is capped - no exposed 5’ppp regions

virnal mRNA has 5’ppp

Question 22

Why can you still respond to viral infection when RIG-I is not present?

Answer 22

Mda-5

Question 23

What is Mda-5?

Answer 23

• similar to RIG-I

- works on picornavirus and caliciviruses

Question 24

Why can RIG-I not detect picornavirus?

Answer 24

5’ppp blocked by IRES and VpG

Question 25

What does Mda-5 recognise and bind to ?

Answer 25

synthetic dsRNA