乙型肝炎病毒（HBV）不仅诱导肝细胞自噬，而且通过自噬促进自身的复制，HBV 编码的X蛋白（HBx）在这过程中发挥了关键作用。高迁徙率族蛋白1（HMGB1）从胞核转位到胞浆后，演变为一种重要的自噬调节蛋白。项目组前期工作报道了肝细胞在LPS等刺激下HMGB1出现胞浆转位，慢性乙型肝炎患者肝细胞也观察到了该现象，但未将HMGB1胞浆转位与HBx诱导的自噬联系起来。为深入阐明HMGB1在HBx诱导肝细胞自噬中的作用及机制，本项目拟用运用免疫共沉淀、基因增强或沉默等探讨HMGB1调控HBx介导的肝细胞自噬的分子机制，并阐明HMGB1介导的自噬对炎性细胞因子释放的影响，最后应用HBx转基因小鼠揭示HMGB1对肝细胞自噬的影响。项目研究不仅有助于揭示HBV激活肝细胞自噬的分子机制，而且为慢性乙型肝炎患者的治疗提供一种新思路。

Autophagy is a catabolic cellular process in which the intracellular components are sequestered into double membrane-bound vesicles that are targeted towards lysosomes for their degradation for energy production. It is a natural process by which the damaged organelles, misfolded proteins and pathogens are cleared from the tissue. It has been shown that Hepatitis B virus survival and its replication requires autophagy, and the induction of an autophagic response enhances viral DNA replication. HBV X protein (HBx) has been shown to induce autophagy, while the mechanism remains relatively poorly defined. .HMGB1 (high mobility group box 1) is normally located in the nucleus, acting as a DNA chaperone involved in the regulation of a number of DNA-associated processes such as replication, transcription, recombination, and repair. The translocation of HMGB1 to the cytoplasm following several autophagic stimuli promotes autophagy through direct interaction with BECN1.Our previous data shown than LPS or TNF-α induced the release of HMGB1 by human liver L02 and HepG2 cells and the process of HMGB1 secretion appeared to be associated with HMGB1 translocation. The HMGB1 translocation was also observed in hepatic cells from chronic hepatitis B patients. However, there is still no report involved both HBx and HMGB1 relationship..In order to clarify the role and mechanism of HMGB1 in HBx induced autophagy in liver cells, Co-Immunoprecipitation, gene enhancement or silencing technology will be applied to explore the mechanism of HMGB1 regulated autophagy, and the effect of autophagy mediated by HMGB1 on the release of inflammatory cytokines will also be studied. Finally, the effect of HMGB1 on autophagy of hepatic cells was revealed by using HBx transgenic mice. Project research not only helps to reveal the molecular mechanism of hepatic autophagy activated by HBV, but also provides a new way for the treatment of chronic hepatitis B patients.