PKR-dependent mechanisms of interferon-alpha for inhibiting hepatitis B virus replication.
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Park IH, Baek KW, Cho EY, Ahn BY
PKR-dependent mechanisms of interferon-alpha for inhibiting hepatitis B virus replication.
Mol Cells. 2011 Aug;32(2):167-72. doi: 10.1007/s10059-011-1059-6. Epub 2011 Jun 23.
- PubMed ID
- 21710204 [ View in PubMed]
- Abstract
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 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-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.