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

Abstract

Interferon-α (IFN-α) 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-α 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-α treatment. Ectopic expression of PKR also resulted in the reduction of viral capsids with concomitant increase of phosphorylated eIF2α. These results suggested that PKR functions as a key mediator of IFN-α in opposing HBV replication, most likely through the inhibition of protein synthesis.

• Authors: Il-Hyun Park, Kyung-Won Baek, Eun-Young Cho, Byung-Yoon Ahn
• Journal: Molecules and cells (Mol Cells) Vol. 32 Issue 2 Pg. 167-72 (Aug 2011) ISSN: 0219-1032 [Electronic] Korea (South)
• PMID: 21710204 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Eukaryotic Initiation Factor-2
• Interferon-alpha
• RNA, Small Interfering
• eIF-2 Kinase

Topics

• Antiviral Agents (pharmacology)
• Capsid (drug effects)
• Cell Line, Tumor
• Eukaryotic Initiation Factor-2 (immunology, metabolism)
• Hepatitis B (drug therapy, immunology, pathology)
• Hepatitis B virus (physiology)
• Humans
• Interferon-alpha (pharmacology)
• Phosphorylation
• RNA, Small Interfering (genetics)
• Signal Transduction (genetics, immunology)
• Transgenes (genetics)
• Virus Replication (genetics)
• eIF-2 Kinase (genetics, immunology, metabolism)