HBV耐药突变可引起病毒生物学特性的改变，还可导致对宿主致病性的改变。我们的研究显示：HBV rtA181T/sW172*突变株所致HBsAg截短突变可引起HBsAg分泌受损，同时还增加肝细胞内HBV的转录与复制水平。.本项目拟利用HBV启动子报告基因体系，观察HBsAg截短蛋白增强HBV转录复制是否与激活HBV启动子有关；利用C启动子HNF4结合位点突变的HBV，以及HBV复制细胞和小鼠模型，观察HBsAg截短蛋白是否通过HNF4激活HBV C启动子活性，从而增强HBV转录复制。通过观察HBsAg截短突变在致细胞病变和小鼠成瘤中的作用，及对HCC发生相关信号通路和宿主蛋白的影响，了解HBsAg截短蛋白在肝癌发生中的可能作用和分子机制。.阐明HBV rtAl81T所致HBsAg截短突变在增强HBV转录复制及对细胞致病性中的分子机制,将有助于阐明HBV耐药株的致病机理。

The drug resistance mutations in hepatitis B virus(HBV) can result in some changes in their biological features and pathogenicity. Our previous study showed that HBV rtA181T/sW172* mutation was not only defective in secretion of HBsAg, but also increased the level of HBV transcription and replication in hepatocytes. .In this project, with HBV promoter reporter gene system, the possible role of HBsAg truncated protein in activating HBV promoter will be investigated. Using C promoter HNF4 binding site mutant HBV, and HBV replication cell culture system and mouse model, the effect of HBsAg truncated protein in enhancing HBV transcription and replication will be classified whether related to activating HBV C promoter through HNF4. Furthermore,by observation the changes of cytopathic, hepatocarcinogenesis, HCC-related signal pathways and host proteins under the influence of HBsAg truncated protein, the possible role and molecular mechanisms of HBsAg truncated protein on HBV will be investigated..The results of this study will be beneficial for understanding the possible role and molecular mechanism of HBsAg truncated protein caused by rtA181T/sW172* mutation in enhancing HBV replication and pathogenesis to host cells.