Regulation of hepatitis B virus gene expression

Human hepatitis B virus (HBV) mainly infects hepatocytes. HB viral gene expression has been demonstrated to be liver-specific using DNA transfection methods. This liver-specific gene expression is regulated by promoter/enhancer elements. HBV contains two enhancer elements. Enhancer element I has been studied in detail at the DNA-protein level. This is further substantiated by DNA transfections of liver and non-liver cell lines with expression plasmids containing enhancer elements controlling the transcription of reporter genes. Genetic analysis of the enhancer elements defined the minimal sequences which play a key role in the regulation of enhancer function. One of the factors binding in this region is RXR alpha. Using only the DNA binding domain of the liver-specific RXR alpha expressed in E. coli, we demonstrated binding of RXR alpha to the putative retinoic acid receptor response element (RARE) in the HBV enhancer. Our studies implicate a potentially important role of retinoic acid and its receptor in the liver-specific regulation of HBV gene expression and the disease pathogenesis associated with infection.