title: Interferon-α suppresses hepatitis B virus enhancer II activity via the protein kinase C pathway.
abstract: HBV has two enhancer (En) regions each of which promotes its own transcription. En II regulates production of pregenomic RNA, a key product of HBV replication, more strongly than En I. Although IFN-α has been found to suppress En I activity, its effect on En II activity has not been examined. Here we used luciferase assay to demonstrate that IFN-α suppresses En II activity. Analysis with several deletion/mutation constructs identified two major segments, nt 1703-1727 and nt 1746-1770, within the En II sequence as being responsible for the suppressive effects of IFN-α. Pre-treatment with protein kinase C (PKC) inhibitors blocked this effect regardless of the expression levels of phospho-STAT1 and Mx upon IFN-α stimulation. These results indicate that IFN-α suppresses En II activity via the PKC pathway, which may be an alternative suppressive pathway for HBV replication. (136 words).
authors: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Takatoshi
authors: T
authors: Nawa
authors: Hisashi
authors: H
authors: Ishida
authors: Tomohide
authors: T
authors: Tatsumi
authors: Wei
authors: W
authors: Li
authors: Satoshi
authors: S
authors: Shimizu
authors: Takahiro
authors: T
authors: Kodama
authors: Hayato
authors: H
authors: Hikita
authors: Atsushi
authors: A
authors: Hosui
authors: Takuya
authors: T
authors: Miyagi
authors: Tatsuya
authors: T
authors: Kanto
authors: Naoki
authors: N
authors: Hiramatsu
authors: Norio
authors: N
authors: Hayashi
authors: Tetsuo
authors: T
authors: Takehara
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D001483:Base Sequence; D045744:Cell Line, Tumor; D004742:Enhancer Elements, Genetic / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D015967:Gene Expression Regulation, Viral; D006515:Hepatitis B virus / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D008969:Molecular Sequence Data; D011493:Protein Kinase C / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014779:Virus Replication
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D011493:Protein Kinase C