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

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.

• Authors: Ju-Il Kang, Shi-Nae Kwon, Se-Hoon Park, Yun Ki Kim, Sang-Yun Choi, Jungsuh P Kim, Byung-Yoon Ahn
• Journal: Virus research (Virus Res) Vol. 142 Issue 1-2 Pg. 51-6 (Jun 2009) ISSN: 0168-1702 [Print] Netherlands
• PMID: 19189853 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Eukaryotic Initiation Factor-2
• Viral Proteins
• eIF-2 Kinase

Topics

• Cell Line
• Eukaryotic Initiation Factor-2 (genetics, metabolism)
• Hepacivirus (genetics, physiology)
• Hepatitis C (enzymology, genetics, virology)
• Humans
• Phosphorylation
• Protein Biosynthesis
• Transcriptional Activation
• Viral Proteins (genetics, metabolism)
• Virus Replication
• eIF-2 Kinase (genetics, metabolism)