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Báo cáo khoa học: Bile acids increase hepatitis B virus gene expression and inhibit interferon-a activity

Hepatitis B virus (HBV) is a 3.2 kb DNA virus that preferentially repli-cates in the liver. A number of transcription factors, including nuclear receptors, regulate the activities of HBV promoters and enhancers. How-ever, the association between these metabolic events and HBV replication remains to be clearly elucidated. | ỊFEBS Journal Bile acids increase hepatitis B virus gene expression and inhibit interferon-a activity Hye Young Kim1 Hyun Kook Cho1 Yung Hyun Choi2 Kyu Sub Lee3 and JaeHun Cheong1 1 Department of Molecular Biology College of NaturalSciences Pusan National university South Korea 2 Department of Biochemistry College of OrientalMedicine Dong Eui University Pusan South Korea 3 Department of Medicine Pusan NationalUniversity South Korea Keywords bile acid FXR gene expression HBV SHP Correspondence J. Cheong Department of Molecular Biology Pusan NationalUniversity Pusan 609-735 South Korea Fax 82 51 513 9258 Tel 82 51 510 2277 E-mail molecule85@pusan.ac.kr Received 19 November 2009 revised 22 March 2010 accepted 26 April 2010 doi 10.1111 j.1742-4658.2010.07695.x 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 farne-soid X receptor a 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-a. Introduction Hepatitis B virus HBV infection is a major worldwide health problem with more than 350 million .