乙型肝炎病毒（HBV）感染是引起国内各种肝脏疾病的主因，控制HBV DNA复制是治疗慢性HBV感染的最佳手段。最近研究显示HBV可以诱导自噬、并利用自噬过程中产生的自噬体膜来促进自身DNA复制。虽然自噬介导HBV DNA复制的分子机制不清，但抑制自噬有利于机体对HBV的清除，提示抑制自噬对HBV治疗具有重要意义。我们前期研究发现p53凋亡刺激蛋白2（ASPP2）能够显著抑制自噬，并对HBV DNA复制、病毒抗原合成和分泌也有明显的抑制能力。因此，我们提出 “ASPP2通过抑制自噬来抑制HBV DNA复制，并最终对HBV感染产生抑制效应”的假说。本课题拟利用细胞和小鼠模型来研究ASPP2抑制自噬介导的HBV DNA复制的相关机制，并在HBV感染患者肝组织标本上验证这一假说，以期阐明ASPP2抑制HBV感染的效应和分子机制，从而为ASPP2基因治疗控制HBV感染的相关研究提供新的研究思路。

Infection by Hepatitis B virus (HBV) causes many types of liver diseases in China, and controlling HBV DNA replication is beneficial for controlling chronic HBV infection. Recently some studies have reported that HBV can induce autophagy and then use autophagosome membrane to enhance its DNA replication. Although how autophagy medicates HBV DNA replication is still unclear, inhibition of autophagy is beneficial for eliminating HBV is reported by many studies, suggesting a critical role of inhibition of autophagy in curing HBV infection. Our previous studies have shown that Apoptosis-stimulating protein of p53-2 (ASPP2) has an ability for inhibiting HBV DNA replication and the production of HBV antigens. According these results, we believe that ASPP2 could inhibit HBV infection by inhibiting autophagy-mediated HBV DNA replication. Here, we will study the mechanisms by which ASPP2 inhibits autophagy-medicated HBV DNA replication in cellular and mouse models and then will verify the mechanisms by using clinical samples. So we will know the effect and mechanisms of ASPP2 on inhibiting HBV infection if we finish this study, which is helpful for researching the effect of ASPP2 gene therapy on curing HBV infection in future.