戊型肝炎病毒（HEV）感染导致妊娠晚期孕妇较高死亡率(>25%)的原因尚不明确。我们前期发现妊娠晚期孕妇血清具有显著促进HEV复制的能力，并且病毒的复制能力随雌激素水平升高而增强，同时HEV感染抑制雌激素受体的表达。据此我们推测妊娠晚期孕妇剧增的雌/孕激素及其激活的雌激素信号通路可能与HEV的复制密切相关。本项目拟从临床HEV感染的孕妇着手，明确HEV在不同妊娠阶段复制能力的差异；并通过添加雌/孕激素类似物或拮抗剂，探讨雌/孕激素对HEV复制的影响；同时过表达雌/孕激素受体或添加拮抗剂，验证HEV感染对雌/孕激素受体表达的影响，并利用免疫共沉淀、免疫荧光法和荧光素酶活性实验探究HEV与雌/孕激素受体的相互作用关系；通过探讨HEV感染对雌激素信号通路及其下游信号通路的影响，揭示妊娠晚期孕妇感染HEV促进病毒复制的作用机制，为进一步揭示HEV感染对孕妇的致病机制提供基础。

The pathogenic mechanism of high mortality (>25%) caused by hepatitis E virus (HEV) infection in pregnant women is unclear. We had confirmed that pregnancy serum facilitates HEV replication in vitro. Meanwhile, HEV replication and the concentration of estrogen is interrelated and dosage dependent. Moreover, HEV replication is involved in the inhibition of estrogen receptor alpha (ERα). Therefore, it is possible that the highly increased estrogen and progestin in the third trimester of pregnancy may promote HEV replication. In the present study, the susceptibility to HEV and the viral titers in HEV-infected pregnant women in their first, second or third trimester of pregnancy will be investigated. Meanwhile, the effects of estrogen/ progestin on HEV replication will be explore by addition of analogues or antagonists of estrogen/progestin in HEV-infected A549 cell. Moreover, the interaction between ERα /ERβ/PR and HEV will be finding out by Co-IP, immunofluorescence assays or luciferase assays. Finally, the mechanism of HEV replication be promoted in pregnant women in their third trimester of pregnancy will be further illuminated by study on estrogen signal pathway, PI3K-Akt or Ras-Raf-ERK signal pathways.