Inhibition of host TYK2 by virus (kw:KW-1112)
Tyrosine kinase 2 TYK2 is a member of IFNα/β signaling that belongs to the Janus kinase (JAK) family. Activation of TYK2 by IFNα/β stimulation leads to a series of phosphorylation events, causing the formation of IFN stimulated gene factor 3 (ISGF3) complexes that consist of STAT1, STAT2 and IFN regulatory factor 9 IRF9. Subsequently, ISGF3 translocates to the nucleus and binds to IFN stimulated response elements (IRF/ISRE), which in turn activates transcription of several hundred IFN-responsive genes.
Several viruses have evolved mechanisms to inhibit TYK2 activity and prevent the subsequent activation of downstream partners STAT1 and STAT2. The Epstein-Barr virus LMP-1 protein interacts with TYK2 and prevents its phosphorylation. Human papillomavirus E6 also interacts with and impair TYK2 activation.
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