title: 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.affiliation: School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Korea.
authors.forename: Il-Hyun
authors.initials: IH
authors.lastname: Park
authors.forename: Kyung-Won
authors.initials: KW
authors.lastname: Baek
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Cho
authors.forename: Byung-Yoon
authors.initials: BY
authors.lastname: Ahn
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D002213:Capsid / Q000187:drug effects; D045744:Cell Line, Tumor; D015852:Eukaryotic Initiation Factor-2 / Q000276:immunology / Q000378:metabolism; D006509:Hepatitis B / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D006515:Hepatitis B virus / Q000502:physiology*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D019076:Transgenes / Q000235:genetics; D014779:Virus Replication / Q000235:genetics; D019892:eIF-2 Kinase / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D000998:Antiviral Agents; D015852:Eukaryotic Initiation Factor-2; D016898:Interferon-alpha; D034741:RNA, Small Interfering; D019892:eIF-2 Kinase