膜融合是许多病毒侵染宿主细胞的关键步骤，对病毒致病机制和抗病毒药物的研究至关重要。尽管HIV的研究一直倍受重视，但对其进入膜融合途径当前存在着巨大争议: 很多研究认为HIV膜融合为发生于细胞表面的直接融合，但最近一些研究认为HIV通过内吞体途径融合；同样，HIV膜融合的生物学和临床意义也有待进一步阐明。本课题旨在研究各种HIV毒株包膜蛋白（Env）介导的膜融合动力学，以期探讨膜融合与HIV传播、疾病进展及抗病毒药物敏感性的相互关系；从膜融合能力和抑制剂敏感性的角度，分析不同HIV毒株的进入膜融合途径；利用序列分析和定点突变，鉴定HIV膜融合功能相关的Env关键基序；通过研究融合蛋白gp41核心结构（6-HB）的热动力学和结构生物学，进一步阐明HIV膜融合动力学和抑制剂作用的分子基础。本课题对揭示病毒持续性感染机制和研发抗病毒药物具有重要的科学意义。

Membrane fusion is a key step of many viruses to infect host cells, and plays critical roles for viral pathogenesis and antiviral therapeutics. Despite considerable efforts, the pathway of HIV entry is highly controversial--while many studies suggest a direct fusion on the cell surface, some recent results suggest a endocytosis pathway. Similarly, the biological and clinical implications of HIV fusion remain to be clarified. The aims of this proposal include: (1) studying the kinetics of diverse HIV Env-mediated fusion to explore the relationships of the membrane fusion and viral transmission, disease progression and drug sensitivity; (2) analyzing the entry pathways of diverse HIV isolates based on the fusion kinetics and antiviral activity; (3) identifying the key Env motifs that determine the fusion by sequencing and mutagenesis; (4) investigating the thermodynamics and structural basis of gp41 core (6-HB) to further understand the mechanisms of fusion kinetics and inhibitors. This project is highly important for revealing the mechanism of viral persistent infection and for developing antiviral drugs.