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

Ju Il Kang, Shi Nae Kwon, Se Hoon Park, Yoon Ki Kim, Sang-Yun Choi, Jungsuh P. Kim, Byung-Yoon Ahn

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)51-56
Number of pages6
JournalVirus Research
Volume142
Issue number1-2
DOIs
Publication statusPublished - 2009 Jun 1

Keywords

  • eIF2α phosphorylation
  • Hepatitis C virus
  • Interferon
  • JFH1
  • PKR
  • Translational control

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases
  • Cancer Research

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