کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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3430061 | 1594396 | 2009 | 6 صفحه PDF | دانلود رایگان |
Hepatitis C virus (HCV) infection is currently treated with IFNα-based therapy but little is known how IFNα inhibits HCV replication. We show here that HCV JFH1 infection of human hepatoma Huh-7 cells leads to the activation of IFN-inducible protein kinase PKR and phosphorylation of the translation initiation factor eIF2α. Compared to a control cell HCV replication was significantly elevated in a PKR-knockdown cell, giving rise to a 10-fold higher viral titer, and was less sensitive to IFNα treatment. Conversely, transient expression of PKR inhibited HCV replication in a kinase-dependent manner with concomitant increase of eIF2α phosphorylation. Further, expression of a phospho-mimetic eIF2α mutant moderately inhibited HCV replication. Together, these results demonstrate that PKR is activated by HCV infection and plays a critical antiviral role through inhibition of viral protein translation.
Journal: Virus Research - Volume 142, Issues 1–2, June 2009, Pages 51–56