乙型肝炎慢性化及治疗应答个体化的机制未完全明确，仍为研究的热点和难点。HBV感染后疾病谱复杂且免疫应答存在异质性。近期研究表明天然免疫特别是NK细胞不仅在宿主防御HBV感染的过程中起着重要作用，并且可以抑制HBV复制。我们前期通过分析慢性HBV感染的不同免疫阶段NK细胞表型、受体及功能是否存在差别，发现活化性受体NKP46在不同组间存在差别，NKP46与HBV DNA、ALT负相关，并且确定了NKP46作为NK细胞的主要杀伤裂解受体，与杀伤功能直接相关。拟在前期研究基础上，采用CBA Flex法分析慢性HBV感染者NKP46信号途径基因表达是否异常并且应用核苷类似物抗病毒治疗后对信号途径基因表达是否有影响，利用流式细胞术检测慢性HBV感染者肝脏内NKP46表达以及通过动物实验体内阻断NKP46观察其抗病毒效应。从天然免疫角度阐明HBV感染慢性化机制，为需找HBV持续感染治疗靶点奠定基础。

The mechanisms of chronity and individual response to treatment in HBV infection are not fully clear and still be the hot and difficult concerns.HBV infection has the characteristics of complex spectrum and the heterogeneity of immune response. Recent studies have shown that innate immunity, especially NK cells, not only play an key role in host defense against HBV infection,but also suppress HBV replication.The function of NK cells depends on the the balance of inhibitory and activating receptors. Preliminary studies found that activatory receptor NKP46 had differences between the different groups,NKP46 had negative correlation with the level of HBV DNA and ALT and NKP46 as the major NK cell lysis receptors was directly related to the killing by the analysis of NK cell phenotype, receptors and function in different immune stages of chronic HBV infection.On the basis of preliminary studies, we aim to analyze the signaling pathway gene expression of NKP46 in chronic HBV infection,the intrahepatic expression of NKP46 in chronic HBV infection patients and test the antiviral effect by blocking the NKP46 in vivo. This has the significance to understand the mechanisms of chronic HBV infection find the therapeutic target.