Inhibition of host STAT1 by virus

The signal transducer and activator of transcription STAT1 protein is a cytoplasmic latent transcription factor that becomes activated by various extracellular stimuli, including cytokines and growth factors that bind to specific cell surface receptors. The activation of STAT1 in IFN-γ and IFN-α/β signaling pathways is largely mediated by phosphorylation of conserved tyrosine and serine residues in the C-terminal region. While IFN-γ induces STAT1 homodimerization, IFN-α/β mainly stimulates heterodimerization of STAT1 and STAT2, both leading to STAT1 activation and nuclear localization.

INFRA1 INFRA2 INFRG1 INFRG2 JAK1 JAK1 TYK2 JAK2 STAT1 STAT1 STAT1 STAT1 STAT1 STAT1 STAT1 STAT2 STAT2 STAT2 STAT2 IRF9 IRF9 IRF9 e1a P vh1 V C

Many viruses modulate the interferon mediated response by acting on STAT1 using different strategies. The V protein of simian virus 5 inhibits interferon signalling by targeting STAT1 for proteasome-mediated degradation. Sendai virus C protein also physically associates with STAT1 and send it to degradation. Vaccinia VH1 phosphatase instead reverses STAT1 activation by interacting with and dephosphorylating STAT1.