J. Virol.：雄激素促进乙肝病毒复制

Enhancement of HBV Replication by Androgen and Its Receptor in Mice

Yongjun Tian, Cheng-fu Kuo, Wen-ling Chen and Jing-hsiung James Ou

Hepatitis B virus (HBV) is an important pathogen that chronically infects more men than women. To understand the molecular mechanism of this gender disparity, we analyzed HBV replication in transgenic mice that carried the HBV genome with or without the ability to express the X protein (HBx). We found that the gender had no effect on HBV surface antigen (HBsAg), DNA and RNA levels in mice before puberty but its effect on HBV after puberty was apparent, with HBV replicating approximately twice more efficiently in male mice than in female mice whether or not the HBx was expressed. The castration of male mice resulted in the reduction of HBV HBsAg, DNA and RNA levels, which could be partially restored by the injection of the androgen agonist R1881, indicating a positive role of androgen in HBV replication. The introduction of the HBV genomic DNA and the androgen receptor (AR) shRNA into the liver of naïve mice by hydrodynamic injection revealed that the effect of androgen on HBV was dependent on its receptor, which apparently could also stimulate HBV replication via an androgen-independent pathway. Further studies indicated that the two previously identified androgen response elements (AREs) in the HBV genome could indeed mediate the effect of androgen on HBV RNA transcription and DNA replication in vivo. These effects of androgen and its receptor on HBV thus provide an explanation to why men have a higher risk for HBV infection than women.