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, Yun Ki Kim, Sang Yun Choi, Jungsuh P. Kim, Byung Yoon Ahn

Research output: Contribution to journalArticlepeer-review

39 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

Bibliographical note

Funding Information:
We thank T. Wakita for kindly providing us with pJFH1. This work was supported by the 21C Frontier Grant for Functional Human Genome Research (FG08-21-22) from the Ministry of Science and Technology of Korea. J.I. Kang, S.N. Kwon, and S.H. Park were supported by the BK21 Graduate Scholarship Program from the Ministry of Education of Korea. J.P. Kim was supported by the Brain Pool program (041S-4-8) of MST of Korea.

Keywords

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

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases
  • Cancer Research

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