Inhibition of host STAT2 by virus

The signal transducer and activator of transcription STAT2 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 STAT2 in IFN-α/β signaling pathways is largely mediated by phosphorylation of conserved tyrosine and serine residues in the C-terminal region. IFN-α/β stimulates heterodimerization of STAT1 and STAT2, leading to STAT2 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 NS1 NS5 V C

Many viruses modulate the interferon mediated response by acting on STAT2. This regulation occurs in many different ways. NS5 protein from Dengue virus mediates STAT2 binding and degradation. Respiratory syncytial virus NS1 protein degrades STAT2 by using the elongin-cullin E3 Ligase. Nipah virus V protein instead prevents STAT2 activation through direct binding but without targeting it to degradation.