Bile acids increase hepatitis B virus gene expression and inhibit interferon-α activity
2010
Kim, Hye Young | Cho, Hyun Kook | Choi, Yung Hyun | Lee, Kyu Sub | Cheong, JaeHun
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 α 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-α.
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