补体2（C2）及其编码基因变异(C2 p.Glu318Asp)影响HBV复制和分泌的机制研究

慢乙肝严重危害人类健康，但其免疫机制未明。本项目拟在本课题组前期关于慢乙肝“遗传机制”研究的基础上，继续深入研究“补体2及其编码基因变异(C2 p.Glu318Asp)” 影响HBV复制和分泌的机制。我们预实验发现：C2在慢乙肝患者肝组织及血中的表达低于健康人，且其肝脏表达与肝脏炎症坏死与纤维化等指标密切相关；C2可通过调节p38-MAPK信号通路影响HBV在HepG2.2.15细胞中的复制和分泌；而HBV感染可通过促进乙酰化的Sp-1表达反过来下调C2表达。因此，我们将进一步构建上调/下调C2与C2 p.Glu318Asp表达的HBV感染的HepG2-NTCP细胞模型，通过比较HBV感染状态的变化，明确C2及其编码基因变异是否会通过影响p38-MAPK信号通路影响HBV的复制和分泌，阐明C2及其编码基因变异影响HBV复制和分泌的机制，为最终明确HBV感染免疫机制提供新的研究途径和基础。

Chronic hepatitis B do serious harm to human health, but the exact immune mechanism still remains unclarified. Based on our previous study about the genetic mechanism of HBV infection, this study aims to discover the effects and mechanism of HBV replication and secretion affected by complement component 2 (C2) and its encoding gene mutation C2 p.Glu318Asp. In the preliminary experiment, we found that C2 expression of liver tissue and peripheral blood of CHB patients were lower than that of healthy controls. C2 expression of liver tissue was closely related to clinical indicators such as inflammatory necrosis index and liver fibrosis index. C2 could affect the replication and secretion of HBV in HepG2.2.15 cells by regulating the p38-MAPK signaling pathway. HBV infection can in turn down-regulate C2 expression by promoting acetylated sp-1 expression.Then on the basis of preliminary experiment, we will further build C2-overexpressing/silencing HBV-infected HepG2-NTCP cells and p.Glu318Asp C2-overexpressing HepG2.2.15 cells and HBV-infected HepG2-NTCP cells to investigate whether C2 and its encoding gene mutation could affect the replication and secretion of HBV by regulating the p38-MAPK signaling pathway. We hope that the mechanism of C2 and its encoding gene mutation to affect the replication and secretion of HBV could be finally revealed, which can provide basis and new strategy to the research of HBV infection immune mechanism.