A possible reason why women generally have lower viral load

StephenW

http://www.ncbi.nlm.nih.gov/pubmed/22240483Gastroenterology. 2012 Jan 9. [Epub ahead of print]
Estrogen Receptor-α Represses Transcription of HBV Genes via Interaction with Hepatocyte Nuclear Factor 4αWang SH, Yeh SH, Lin WH, Yeh KH, Yuan Q, Xia NS, Chen DS, Chen PJ.
SourceDepartment of Microbiology, National Taiwan University College of Medicine, Taipei, Taiwan.

AbstractBACKGROUND & AIMS: Women with hepatitis B virus (HBV) infection usually have lower viral loads than men, reducing their risk for liver cancer. There are two androgen-responsive elements in the HBV enhancer I, which contribute to higher viral titers in men. We investigated whether and how estrogen signaling interacts affects progression of HBV infection.
METHODS: Ovariectomy and estrogen supplementation were used to evaluate the effect of estrogen on HBV titers in transgenic mice with replicating HBV in hepatocytes. The effect of estrogen signaling on transcription of HBV genes, and the mechanisms of regulation, were studied in HepG2 cells.
RESULTS: HBV titers increased in female mice after ovariectomy and decreased in male mice supplemented with estrogen. Hepatic expression of estrogen receptor (ER)α was increased by estrogen exposure. In HepG2 cells, upregulation of ERα reduced HBV transcription, which required a specific region within enhancer I. Direct DNA-binding of ERα and histone deacetylase activity were not required for ERą-mediated repression of HBV genes. Overexpression of hepatocyte nuclear factor (HNF)4α, which binds to this region, overcame the repressive effect of ERα. ERα did not repress transcription of an HBV replicon with a mutant HNF4ą-binding site within enhancer I. Co-immunoprecipitation assays demonstrated an interaction between ERą and HNF4α; this interaction prevented HNF4ą binding to enhancer I and activation of HBV transcription.
CONCLUSIONS: Estrogen can repress transcription of HBV genes by upregulating ERα, which interacts with and alters binding of HNF4α to the HBV enhancer I. These findings might account for the lower viral load and reduced incidence of liver cancer in HBV-infected women than men.

StephenW

消化科。 2012年1月9日。 [检索提前打印]
雌激素受体α压抑通过相互作用与肝细胞核因子4αHBV基因的转录
王少怀，叶上海，林文汇，叶锦，Q圆，夏NS，陈德尚，陈PJ。
来源

微生物学系，国立台湾大学医学院，台北，台湾。
摘要
背景及目的：

与乙型肝炎病毒（HBV）感染的妇女通常比男性低病毒载量，减少他们对肝癌的风险。有两个雄激素应答元件在HBV增强剂我，这有助于男性较高的病毒滴度。我们调查是否和如何雌激素信号交互影响HBV感染的进展。
方法：

卵巢切除和雌激素补充用于评估转基因小鼠肝细胞中HBV复制的雌激素对乙肝病毒滴度的影响。雌激素信号对乙肝病毒基因的转录和调控机制的影响，在HepG2细胞进行了研究。
结果：

乙肝病毒滴度增加雌性小鼠卵巢切除后，在与雌激素补充雄性小鼠减少。肝“雌激素受体（ER）α的表达增加雌激素暴露。在HepG2细胞中，ERα的上调减少乙肝病毒的转录，这需要一个特定区域内增强剂一直接的DNA结合ERα和组蛋白去乙酰化酶活性并不需要ERA -介导的HBV基因的镇压。过表达肝细胞核因子（HNF）4α，结合本地区，克服了ERα的镇压效果。并没有抑制ERα的乙型肝炎病毒复制子的转录增强剂一突变HNF4ą结合现场免疫共沉淀分析表明ERA和HNF4α之间的相互作用，这种相互作用阻止HNF4ą约束力增强剂我和乙肝病毒转录激活。
结论：

通过上调ERα的，交互和改变HNF4α约束力HBV的增强一，这些研究结果可能会考虑降低病毒载量和降低肝癌的发病率在乙肝病毒感染的妇女比男性雌激素可以抑制乙肝病毒基因的转录。

咬牙硬挺

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