慢性乙肝严重危害人类健康，干扰素对其疗效并不确定且其抗HBV机制未明。本项目在本课题组前期关于慢性乙肝的“遗传机制”的研究基础上，继续深入研究“干扰素编码基因变异（IFNA2 p.Ala120Thr）”降低IFN-α2抗HBV感染能力、导致细胞对HBV更加易感的可能机制。本项目使用“慢病毒转染及过表达”、“蛋白表达纯化”、“QPCR”等成熟技术，构建p.Ala120Thr突变型干扰素，建立HepG2-NTCP细胞模型，观察该变异干扰素在该细胞模型中抗HBV感染能力的变化；构建各种变异体干扰素，比较它们抗HBV感染能力的差异；最后检测该干扰素编码基因变异在HBV感染细胞过程中导致的抗HBV效应蛋白的变化，对APOBEC3相关信号通路和基因表达的影响，阐明“IFNA2 p.Ala120Thr”降低干扰素抗HBV感染能力的机制，为最终明确干扰素抗HBV感染的机制提供新的研究途径和基础。

Hepatitis B do serious harm to human health. Therapeutic effects of interferon is uncertain with mechanism not been clarified. Based on our previous study about the genetic mechanism of HBV infection, this study is to discover the effects and mechanism of more susceptibility to HBV infection induced by interferon gene mutation IFNA2p.Ala120Thr. Some well-handling techniques were used in this research including lentivirus transfection, gene over-express, protein expression and purification, immunohistochemistry, QPCR and so on. We will build p.Ala120Thr mutant interferon and HepG2-NTCP celline. And we want to investigate how p.Ala120Thr affect the anti-HBV ability of interferon on HepG2-NTCP which we have constructed. After that, we constructed other mutant interferon based on p.Ala120Thr and compare their different ability of anti-HBV. At last, we will investigate the possible mechanism of it, which might be explained by anti-HBV effect protein, APOBEC3 signal transduction and gene expression, in order to provide methods and basis for mechanism research of interferon’s anti-HBV effects.