title: Bile acids increase hepatitis B virus gene expression and inhibit interferon-alpha activity.
abstract: Hepatitis B virus (HBV) is a 3.2 kb DNA virus that preferentially replicates in the liver. A number of transcription factors, including nuclear receptors, regulate the activities of HBV promoters and enhancers. However, the association between these metabolic events and HBV replication remains to be clearly elucidated. In the present study, we assessed the effects of bile acid metabolism on HBV gene expression. Conditions associated with elevated bile acid levels within the liver include choleostatic liver diseases and an increased dietary cholesterol uptake. The results obtained in the present study demonstrate that bile acids promote the transcription and expression of the gene for HBV in hepatic cell lines; in addition, farnesoid X receptor alpha and the c-Jun N-terminal kinase/c-Jun signal transduction pathway mediate the regulatory effect of bile acids. Furthermore, an orphan nuclear receptor, small heterodimer partner protein, is also involved in the bile acid-mediated regulation of HBV gene expression. The bile acid-mediated promotion of HBV gene expression counteracts the antiviral effect of interferon-alpha.
authors.affiliation: Department of Molecular Biology, College of Natural Sciences, Pusan National University, Pusan, South Korea.
authors.forename: Hye Young
authors.initials: HY
authors.lastname: Kim
authors.forename: Hyun Kook
authors.initials: HK
authors.lastname: Cho
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
authors.forename: Kyu Sub
authors.initials: KS
authors.lastname: Lee
authors.forename: JaeHun
authors.initials: J
authors.lastname: Cheong
mesh_terms: D001647:Bile Acids and Salts / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D016898:Interferon-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D001647:Bile Acids and Salts; D016898:Interferon-alpha