根据发表在2012年2月那期Journal of Virology期刊上的一篇新论文，雄激素(androgen)促进乙型肝炎病毒(hepatitis B virus, HBV)复制，使得男性要比女性更加容易遭受这种病毒的攻击。 来自美国南加州大学的James Ou说，“我们的研究允许我们理解HBV携带者的性别差异，以及为什么这种病毒往往导致男性患上的肝疾病严重性要比女性高。” 研究人员发现在青春期前的雄性和雌性小鼠中的HBV水平不存在差别。Ou说，然而，青春期之后，雄性小鼠身上的HBV水平超过雌性小鼠，而且在某些情形下超过2倍。随后对雄性小鼠进行阉割导致HBV病毒载量下降，但是给遭阉割的小鼠注射雄激素激动剂(androgen agonist)能够再次导致病毒载量上升。 在第三组实验中，研究人员通过基因敲除手段移除雄激素受体，又一次废除了雄激素在HBV复制上发挥的影响。研究人员进一步研究还发现宿主激活的雄激素受体识别HBV基因组内的序列元件，经识别后就促进HBV基因表达和复制。 流行病学研究研究已证实男性成为HBV携带者的可能性是女性的3到7倍，男性HBV携带者也比女性更容易产生肝癌。 Ou说，“HBV是人类最为重要的病原体之一。全世界大约有3.5亿人是HBV慢性感染的，其中每年大约有100万人死亡。” HBV能够通过性传播，也可通过没有消毒的针头传播，另外在围产期(perinatally)母亲也会传给胎儿。在一些地方性HBV流行的区域，它经常在年轻小孩之间传播。它存在于血液(包括女性经血)、阴道分泌物、唾液、精液和乳汁之中，而且在其他体液中也存在，但是含量较低。不过人们可以接种疫苗抵抗HBV感染。
doi:10.1128/JVI.06707-11
PMC:
PMID:
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.
| 
发表于 2012-2-20 22:31
