PKR protein kinase is activated by hepatitis C virus and inhibits viral replication through translational control.

Article Details

Citation

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.

PubMed ID
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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Interferon-induced, double-stranded RNA-activated protein kinaseP19525Details