title: Transactivation of the hepatitis B virus core promoter by the nuclear receptor FXRalpha.
abstract: Hepatitis B virus (HBV) core promoter activity is positively and negatively regulated by nuclear receptors, a superfamily of ligand-activated transcription factors, via cis-acting sequences located in the viral genome. In this study, we investigated the role of farnesoid X receptor alpha (FXRalpha) in modulating transcription from the HBV core promoter. FXRalpha is a liver-enriched nuclear receptor activated by bile acids recognizing hormone response elements by forming heterodimers with retinoid X receptor alpha (RXRalpha). Electrophoretic mobility shift assays demonstrated that FXRalpha-RXRalpha heterodimers can bind two motifs on the HBV enhancer II and core promoter regions, presenting high homology to the consensus (AGGTCA) inverted repeat FXRalpha response elements. In transient transfection of the human hepatoma cell line Huh-7, bile acids enhanced the activity of a luciferase reporter containing the HBV enhancer II and core promoter sequences through FXRalpha. Moreover, using a greater-than-genome-length HBV construct, we showed that FXRalpha also increased synthesis of the viral pregenomic RNA and DNA replication intermediates. The data strongly suggest that FXRalpha is another member of the nuclear receptor superfamily implicated in the regulation of HBV core promoter activity and that bile acids could play an important role in the natural history of HBV infection.
authors.affiliation: INSERM U851, Université de Lyon, Lyon, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Ramière
authors.forename: Caroline
authors.initials: C
authors.lastname: Scholtès
authors.forename: Olivier
authors.initials: O
authors.lastname: Diaz
authors.forename: Vinca
authors.initials: V
authors.lastname: Icard
authors.forename: Laure
authors.initials: L
authors.lastname: Perrin-Cocon
authors.forename: Mary-Anne
authors.initials: MA
authors.lastname: Trabaud
authors.forename: Vincent
authors.initials: V
authors.lastname: Lotteau
authors.forename: Patrice
authors.initials: P
authors.lastname: André