慢性乙型肝炎是常见的病毒性肝炎，其发病机制仍不明确。研究表明乙型肝炎病毒与人类基因融合可能是慢乙肝疾病进展重要原因。我们发现，乙肝病毒可以与ESPL1基因发生融合形成HBV S-Human ESPL1，该融合基因在乙肝相关肝癌患者中可高频检出。ESPL1表达的分离酶不能分泌出细胞，但我们预实验发现HBV S-Human ESPL1可产生能分泌出细胞的融合蛋白，且与肝癌发生有密切联系。因此我们推测基因融合可能改变了ESPL1的固有特性。本课题拟从细胞、动物和临床水平研究该融合基因的特异性。构建细胞和动物模型，采用分子、形态和细胞学方法观察该融合基因及其转录因子在各模型中的表达水平、蛋白修饰、功能特性，结合聚合酶链式反应、蛋白印迹、质谱检测技术，系统解析HBV S-Human ESPL1在慢乙肝进程中具体作用及分子机制。这将增进我们对乙肝发病机制的新认识，为开发融合基因靶点药物提供科学参考。

Chronic hepatitis B is a common viral hepatitis which caused by hepatitis B virus. However, the molecular and cellular mechanisms underlying its pathogenesis remain largely unclear so far. Studies have shown that the fusion of hepatitis B virus and human gene may be an important cause of disease progression. ESPL1 is a gene encoding and expressing Separase, which is the only protein that can isolate sister chromatids. In our preliminary experiments, it has been shown that hepatitis B virus can fuse with ESPL1 to form HBV S-Human ESPL1, which can be detected at high frequency in patients with hepatitis B virus-related hepatocellular carcinoma. Separase cannot be secreted out of cells, but we found that HBV S-Human ESPL1 can express fusion protein, which can be secreted out of cells and is closely related to the occurrence of hepatocellular carcinoma. We speculate that gene fusion may alter the intrinsic properties of ESPL1. In order to validate this speculation, We intend to study the expressional level, protein modification and functional characteristics of the fusion gene and its transcriptional factors in cell and animal models by molecular, morphological and cytological methods at cell, animal and clinical levels. We plan to apply polymerase chain reaction, Western blot, and protein mass spectrometry to systematically analyze the specific role and molecular mechanism of HBV S-Human ESPL1 in the process of chronic hepatitis B. This study will enhance our new understanding of the pathogenesis of hepatitis B and provide a scientific basis for the prevention and treatment of hepatocellular carcinoma and the development of targeted drugs for this fusion gene.