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 language | English |
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Pages (from-to) | 167-172 |
Number of pages | 6 |
Journal | Molecules and cells |
Volume | 32 |
Issue number | 2 |
DOIs | |
Publication status | Published - 2011 Aug |
Keywords
- Antiviral mechanism
- Hepatitis B virus
- IFN-a
- PKR
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology