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 language | English |
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Pages (from-to) | 51-56 |
Number of pages | 6 |
Journal | Virus Research |
Volume | 142 |
Issue number | 1-2 |
DOIs | |
Publication status | Published - 2009 Jun |
Keywords
- Hepatitis C virus
- Interferon
- JFH1
- PKR
- Translational control
- eIF2α phosphorylation
ASJC Scopus subject areas
- Virology
- Infectious Diseases
- Cancer Research