氧化还原蛋白AMPK通过细胞自噬调控HBV复制的分子机制研究

Hepatitis B virus (HBV) is a common pathogen that represents a severe public health burden. Thus, it is urgently required to clarify the underlying mechanism of HBV production to improve the survival rate and quality of life for patients with HBV infection. AMPK is a well-known key regulator of the cellular energy metabolism, and acts as an important sensor for oxidative stress. In our preliminary studies, we have found that AMPK is activated in response to HBV-induced oxidative stress, which in turn decreases the production of HBV. Further studies suggest that autophagy might be involved in AMPK-mediated HBV production. Accordingly, this study intends to focus on the molecular mechanisms by which AMPK inhibits HBV production through regulating the autophagy process. Furthermore, this project will evaluate the antiviral effects by combining AMPK activator with autophagy inhibitor. This study will lead to a better understanding of the cellular responses under HBV infection, and provide new insights for the further improvement of clinical outcomes of HBV infection.

乙型肝炎病毒（hepatitis B virus，HBV）是一种严重威胁人类健康的病原体，其复制机理复杂，需要不断拓展新思路逐步加以阐明。AMPK是细胞内调节能量代谢的关键分子，也是胞内氧化应激的重要感应蛋白之一。在前期研究中，我们发现HBV诱导的宿主细胞氧化应激介导了AMPK的氧化还原调控和磷酸化激活，而活化的AMPK却反过来成为HBV复制的限制因子，抑制了HBV复制。进一步的研究提示，AMPK可能通过调控细胞自噬干预HBV复制过程。本项目拟在前期工作的基础上，阐明AMPK通过细胞自噬调控HBV复制的分子机制，并利用HBV病毒复制的细胞及动物模型评价AMPK激动剂联合细胞自噬抑制剂的抗病毒效果。本项目的实施将有助于进一步阐明宿主细胞与HBV相互作用的分子机制，为发展更高效的抗病毒策略提供新的思路。

乙型肝炎病毒（hepatitis B virus，HBV）是一种严重威胁人类健康的病原体，其发病机理复杂，迫切地需要进一步解析病毒致病的分子机理并发展新型高效的治疗策略。AMPK是细胞内调控能量代谢的关键分子，也是胞内氧化应激的重要感应蛋白之一。我们的研究发现HBV诱导的宿主细胞氧化应激可介导AMPK的氧化还原调控及磷酸化激活，而活化的AMPK却反过来成为HBV复制的限制因子，抑制了病毒的复制。进一步的研究表明，细胞自噬在AMPK抑制HBV增殖中发挥重要的作用。激活的AMPK通过增加细胞内ATP水平来促进自噬溶酶体的降解及自噬泡的消耗，导致HBV病毒增殖的抑制。综上所述，我们的研究结果表明，AMPK作为宿主细胞应对HBV病毒感染的调节因子，可通过促进细胞自噬降解来限制病毒的产生。该研究阐明了一种新的宿主细胞应对 HBV 感染的分子机制，为发展更高效的抗病毒策略提供了新的思路。