Interferons

Question 0

Type 1 -IFN

Answer 0

Are rapidly induced by virus infection of any cell type (triggered by eg high amounts of dsRNA), activation of TLR infection of plasmacytoid DCs

Question 1

Interferons

Answer 1

• group of secreted proteins that induce an antiviral state in uninflected cells by interfering with viral replication
• very direct signal transfer involving Janus kinase and signal transduction and activator if transcription
• STATs bind to promoters inducing >40 gene products that contribute to the antiviral state

Question 2

Type 2 IFN

Answer 2

IFN gamma is produced by NK cells CD4 TH1 and CD8 T effector cells

Question 3

Interferon induced signalling pathway

Answer 3

• two separate alpha interferon receptors - Tyk2 and Jak1
• binding of interferon cross links adjacent receptors and Jaks cross phosphorylate each other on tyrosine
• activated Jaks phosphorylate receptor on tyrosine
• after STATs dock on specific phosphotryosines on the receptor, the Jaks phosphorylate them
• STATs dissociate from receptor and dimerises via their sh2 domain
• StAts migrate to nucleus bind to DnA and other gene regulatory proteins
• blocks protein synthesis

Question 4

Antiviral state

Answer 4

1) + dsRNA phosphorylates elF-2alpha > stops translation
2) activates NF-kB transcription factor > inflammatory response
3) apoptosis
Increase of RNaseL and cause degradation of RNA

Activates PKR > stimulates synthesis of inactive 2,5-A synthetase by activating RNase

Question 5

Influenza

Answer 5

• influenza virus activates the p58 pathway of the host cell which blocks the activation of PKR - variety of ways
• normally p58 prevent in all inactive
• NSI blocks the dsRNA dependent apoptotic pathway
• NSI interacts directly with PKR to inhibit the kinase function may also act at other steps