Microbiology 1: Interferon

Question 1

Define “interferon”

Answer 1

Soluble cytokine produced when cells are exposed to a virus that stimulates de novo transcription of IF-stimulated genes to cause a cytokine storm

Question 2

What is the general stimulus for IFN production?

Answer 2

PAMP recognition

Question 3

What element of a virus acts as a PAMP?

Answer 3

Viral nucleic acid

Question 4

What sort of PRR is found in the cytoplasm?

Answer 4

Rig-1 like receptors (RLRs)

Question 5

What sort of PRR is found in endosomes?

Answer 5

Toll-like receptors (TLRs)

Question 6

Recall the site of production of each subtype of type 1 IFN

Answer 6

IFN-alpha = plasmacytoid dendritic cells
IFN-beta = all cells

Question 7

Recall the TF that leads to the production of each of the subtypes of type 1 IFN

Answer 7

Alpha = IRF7
Beta = IRF3

Question 8

Where is the IFN-alpha receptor present?

Answer 8

All tissues

Question 9

Describe the structure of the IFNAR

Answer 9

Heterodimer

Question 10

Through which receptor does each of the subtypes of tye 1 IFN signal?

Answer 10

IFNAR

Question 11

Which type of IFN is always first to be made?

Answer 11

Type 1 IFN Beta

Question 12

What is the function of IFN beta?

Answer 12

Indices anti-viral state i neighbouring cells

Question 13

Recall the 3 major functions of type 1 IFN

Answer 13

Induce antimicrobial state
Modulate innate immunity
Activate adaptive immunity

Question 14

How many isotypes are there of each of the subtypes of tye 1 IFN?

Answer 14

IFN alpha has 13

IFN beta has 1

Question 15

What type of IFN is type2 IFN?

Answer 15

IFN gamma

Question 16

Through which receptor does IFN gamma signal?

Answer 16

IFNGR

Question 17

By what sort of cells is IFN gamma produced?

Answer 17

T cells

NK cells

Question 18

What type of IFN is type 3 IFN?

Answer 18

IFN lambda

Question 19

Through which receptors does IFN lambda signal?

Answer 19

IL28R amd IL10-beta

Question 20

Where are IFN-lambda receptors expressed?

Answer 20

Epithelia

Question 21

What is the main function of IFN lambda?

Answer 21

Protect barriers of body - especially important in liver defence against Hep B/C

Question 22

Recall the pathway that leads to the transcription of IFN alpha in the presence of RNA viruses

Answer 22

1. Virus enters endosome in cell
2. PAMP recognition by TLR in endosome
3. IFNalpha gene switched on

Question 23

Recall a protective factor that cells may express against influenza virus?

Answer 23

IFITM3

Question 24

What is IFITM3?

Answer 24

Prevents virus releasing its genome into the next cell

Question 25

Recall the pathway that leads to the transcription of IFN beta in the presence of RNA viruses

Answer 25

1. RNA recognised by RLR in cytoplasm 2. RIG-1 signalls thorugh MAVS on mitochondrion 3. IRF3 expressed --> transcription of IFN beta gene

Question 26

Recall the steps of IFN transcription initiated by DNA viruses

Answer 26

1. Sensed in nucleus by cGAS 2. cGAS --> cGAMP 3. Sting activated 3. IFN beta produced

Question 27

What is the main moderator of the IFN response?

Answer 27

SOCS

Question 28

What does SOCS stand for?

Answer 28

Suppressor Of Cytokine Signalling genes

Question 29

Recall 4 examples of ISGs

Answer 29

PKR 2'5'OAS Mx ASAR

Question 30

What is the function of the protein encoded by PKR?

Answer 30

Inhibition of translation (cell's "altruistic" response)

Question 31

What is the function of the protein encoded by Mx?

Answer 31

Mx1 inhibits influenza genome | Mx2 inhibits HIV genome

Question 32

Recall 5 mechanisms of viral evasion of IFN response

Answer 32

1. SOCS switched on rapidly 2. PAMP concealed 3. Rapid replication to outpace response 4. IFN blockade 5. Gene expression change

Question 33

How does Hep C evade the viral response?

Answer 33

Produces NS3/4 which can cleave MAVS

Question 34

How does H1N1 flu evade the T1 IFN response?

Answer 34

Binds RIG-1

Question 35

How does Ebola evade the T1 IFN response?

Answer 35

Produces VP proteins that block RIG1 and STAT

Question 36

Recall 3 RNA viruses that can specifically evade T1 IFN

Answer 36

Hep C Ebola H1N1 flu

Question 37

How do DNA viruses tend to evade the T1 IFN response? Give an example of a virus that does this

Answer 37

Encode soluble cytokine receptors to "mop up" IFN eg POX VIRUSES

Question 38

Recall 4 hopes for therapies utilising IFN

Answer 38

1. Mimick Pox virus - produce soluble cytokines 2. IFN lambda as an antiviral 3. Live attenuated vaccines using viruses that are unable to control IFN 4. May be used to treat cancer

Question 39

Recall the immediate downstream signalling pathway of IFN receptors

Answer 39

Dimerise to activate STAT