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

    25 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

    Bibliographical note

    Funding Information:
    We thank W.S. Ryu for kindly p roviding us with p HBV1.2. This work was sup p orted by the Health Technology Research Grant (#A080599) from the Ministry of Health, Welfare and Family Affairs of the Rep ublic of Korea.

    Keywords

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

    ASJC Scopus subject areas

    • Molecular Biology
    • Cell Biology

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