Inhibition of the interferon-inducible protein kinase PKR by HCV E2 protein

Most isolates of hepatitis C virus (HCV) infections are resistant to interf eron, the only available therapy, but the mechanism underlying this resista nce has not been defined. Here it is shown that the HCV envelope protein E2 contains a sequence identical with phosphorylation sites of the interferon -inducible protein kinase PKR and the translation initiation factor eIF2 al pha, a target of PKR. E2 inhibited the kinase activity of PKR and blocked i ts inhibitory effect on protein synthesis and cell growth. This interaction of E2 and PKR may be one mechanism by which HCV circumvents the antiviral effect of interferon.