乙型病毒性肝炎由乙肝病毒（HBV）感染引起，与肝硬化、肝癌的发生密切相关，目前仍缺乏有效的防治措施。干扰素诱导蛋白MxA可有效抑制HBV复制，但抑制机理尚不明确。我们前期研究发现，MxA蛋白可通过与病毒核衣壳蛋白HBc相互作用抑制HBV复制（Hepatology, 2012），提示MxA蛋白可能干扰病毒核衣壳的组装。本项目拟进一步确认和研究该机制，首先采用非变性蛋白印迹、蔗糖密度梯度离心等技术明确MxA蛋白抑制病毒核衣壳的组装；进而通过免疫共沉淀、体外蛋白互作和分子对接等生化和计算生物学手段，鉴定MxA与HBc相互作用的模式和位点；最终验证HBc上这些位点为核衣壳组装所必需。本研究旨在阐明MxA蛋白通过与核衣壳蛋白HBc相互作用干扰病毒核衣壳的组装抑制HBV复制的分子细胞学机制，为HBV感染的临床干预提供新线索，为将MxA蛋白开发成新一类抗HBV药物奠定基础，具有重要的临床意义。

Hepatitis B virus (HBV) infection is a global public health problem, with the high risk for progressing to chronic hepatitis, cirrhosis, and hepatocellular carcinoma. So far it is lack of effective therapeutic intervention against HBV. Human MxA, an interferon-inducible crucial antiviral protein, can significantly inhibit HBV replication. However, the molecular mechanism underlying the anti-HBV activity of MxA remains largely unknown. We have found that MxA inhibits HBV replication by interaction with core protein HBc as reported previously (Hepatology, 2012), implying a mechanism of interfering with core particle assembly. In this project, we plan to further investigate and confirm the mechanism, identify the mode and the critical amino acid sites of the interaction between MxA and HBc, and verify the essenciality of the critical amino acid sites of HBc for core particle assembly, widely using native gel electrophoresis, sucrose-gradient centrifugation, immunoprecipitation, in vitro protein interaction, molecular docking and other biochemistry or computational biology methods. Our project will suggest a previously unrecognized molecular mechanism of MxA anti-HBV, offering a potential target for future anti-HBV drug design and providing a promising strategy for HBV infection in clinical treatment.