Inhibition of host interferon receptors by virus

Type I interferons play an essential role in maintaining a defense against viral infection. These cytokines also participate in the control of cell proliferation. These effects are triggered by ligand binding to a specific cell surface receptor. IFN receptors (IFN-R) are composed of two chains, α and β, and transduce signals via the classical Jak-Stat pathway.

INFRA1 INFRA2 INFRG1 INFRG2 JAK1 JAK1 TYK2 JAK2 STAT1 STAT1 STAT1 STAT1 STAT1 STAT1 STAT1 STAT2 STAT2 STAT2 STAT2 IRF9 IRF9 IRF9 K3

Several viruses induce the ER stress response also named the unfolded protein response (UPR). Such activation requires the endoplasmic reticulum resident protein kinase PERK. The activation of this pathway promotes phosphorylation- dependent ubiquitination and degradation of IFNAR1, specifically inhibiting type I IFN signaling and antiviral defenses.