KMID : 0578320110320020167
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Molecules and Cells 2011 Volume.32 No. 2 p.167 ~ p.172
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PKR-Dependent Mechanisms of Interferon-¥á for Inhibiting Hepatitis B Virus Replication
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Park Il-Hyun
Baek Kyung-Won Cho Eun-Young Ahn Byung-Yoon
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Abstract
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Interferon-alpha (IFN-alpha) 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-alpha 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 spe-cifically suppressed through RNA-interfer-ence. Intracellular level of viral capsids was down-regu-lated likewise in a PKR-dependent manner, whereas that of HBV transcripts including the viral RNA pregenome was not affected by IFN-alpha treatment. Ectopic expression of PKR also resulted in the reduction of viral capsids with concomitant increase of phosphorylated eIF2alpha. These results suggested that PKR functions as a key mediator of IFN-alpha in opposing HBV replication, most likely through the inhibition of protein synthesis.
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KEYWORD
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antiviral mechanism, Hepatitis B virus, IFN-¥á, PKR
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