PKR-dependent mechanisms of interferon-a for inhibiting hepatitis B virus replication

Il Hyun Park, Kyung Won Baek, Eun Young Cho, Byung Yoon Ahn

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Interferon-a (IFN-a) inhibits the replication of hepatitis B virus (HBV) in vivo and in vitro, but the molecular mechanism of this inhibition has been elusive. We found that while HBV replication in transfected human hepatoma Huh-7 cell was severely inhibited by IFN-a treatment as reported previously, this inhibition was markedly impaired in the cell in which the expression of IFN-inducible, double- stranded RNA-dependent protein kinase (PKR) was stably and specifically suppressed through RNA-interference. Intracellular level of viral capsids was down-regulated likewise in a PKR-dependent manner, whereas that of HBV transcripts including the viral RNA pregenome was not affected by IFN-a treatment. Ectopic expression of PKR also resulted in the reduction of viral capsids with concomitant increase of phosphorylated eIF2a. These results suggested that PKR functions as a key mediator of IFN-a in opposing HBV replication, most likely through the inhibition of protein synthesis.

Original languageEnglish
Pages (from-to)167-172
Number of pages6
JournalMolecules and cells
Volume32
Issue number2
DOIs
Publication statusPublished - 2011 Aug

Keywords

  • Antiviral mechanism
  • Hepatitis B virus
  • IFN-a
  • PKR

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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