目前，宿主控制HBV复制的机制尚未完全清楚。在我们的前期工作中，采用Affymetrix RNA芯片，分析了83例慢性HBV感染患者肝组织的基因表达谱，首次发现FAM176A基因在非活动期患者肝组织内的表达水平明显高于免疫耐受期患者，并与血清HBV DNA水平呈负相关。在体外实验中，过表达FAM176A可显著抑制HBV的复制，而沉默该基因后可上调HBV复制，但其机制尚不清楚。我们推测，FAM176A有可能通过调节肝细胞的自噬功能而影响HBV的复制。本课题拟在肝癌细胞系和高压尾静脉注射建立的小鼠慢性HBV感染模型中验证FAM176A对HBV复制的抑制作用，了解该抑制作用是否通过调节肝细胞的自噬功能而实现，并在不同临床类型的慢性HBV感染患者肝组织中，验证其表达水平是否和病毒载量以及细胞自噬相关，以阐明肝细胞内FAM176A抑制HBV复制的机制。本研究有助于揭示宿主基因控制HBV复制的新机制。

So far,the host defense factors against HBV replication remain unclear. From our previous study, we analyzed 83 chronic hepatitis B virus infected patients by Affymetrix GeneChip arrays and found that the expression level of FAM176A gene in inactive carrier patients was significantly higher than in the immune tolerance patients, which was inversely associated with the level of serum HBV DNA.In vitro study showed that overexpress of FAM176A gene could significantly inhibit HBV replication, while knockdown of FAM176A gene could upregulate HBV replication, the mechanism is still unknown. We hypothesize that FAM176A can influence HBV replication through the regulation of liver cell autophagy function. This project will also verify whether FAM176A could inhibit HBV replication in liver cancer cell lines or high-pressure tail vein injection mouse model and whether the FAM176A expression level has a correlation with viral load or cell autophagy in the liver tissue of chronic hepatitis B virus infected patients. This study will help to uncover the new mechanism that host factor can control HBV replication..