PKR protein kinase is activated by hepatitis C virus and inhibits viral replication through translational control.
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Kang JI, Kwon SN, Park SH, Kim YK, Choi SY, Kim JP, Ahn BY
PKR protein kinase is activated by hepatitis C virus and inhibits viral replication through translational control.
Virus Res. 2009 Jun;142(1-2):51-6. doi: 10.1016/j.virusres.2009.01.007. Epub 2009 Feb 2.
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- 19189853 [ View in PubMed]
- Abstract
Hepatitis C virus (HCV) infection is currently treated with IFNalpha-based therapy but little is known how IFNalpha 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 eIF2alpha. 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 IFNalpha treatment. Conversely, transient expression of PKR inhibited HCV replication in a kinase-dependent manner with concomitant increase of eIF2alpha phosphorylation. Further, expression of a phospho-mimetic eIF2alpha 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.