已证明HIV-1的衣壳是由衣壳蛋白（CA）的二聚体、五聚体和六聚体等基本结构单位组装而成，但衣壳如何组装以及组装过程存在怎样的功能表位等问题仍悬而未决，基于CA蛋白的靶点研究成为HIV的研究热点之一。在上期国家自然科学基金资助下我们获得一种天然HIV突变株CA的独特二聚体晶体结构，是由Cys177相互形成二硫键介导，功能研究显示该二聚体存在于病毒粒子中，可能锁住了CA蛋白特殊的二聚体构象，为CA五聚体和六聚体进一步形成HIV衣壳提供了新的连接方式。本研究拟在此基础上进一步研究Cys177位点对病毒复制和感染能力的影响，设计多级二硫键的CA蛋白，研究HIV衣壳的组装机理；构建突变HIV假病毒/病毒，利用已有的单抗盘检测表位变化，从而鉴定功能表位，使用X-ray晶体衍射和低温电镜结构重建方法解析CA蛋白及免疫复合物结构，以期为基于CA的HIV研究（如抗病毒治疗、疫苗设计等）提供结构信息和思路。

It is evident that HIV-1 capsid is made of dimeric,pentameric and hexameric CA blocks. Otherwise, how the capsid assemble from intermedia components? what is functional epitope present in assembly procedure? These puzzles remain unclear, which is hot-spot in HIV research art. Supported by previous NSFC project, we sovle the crystal structure of CA dimer derived from an HIV native muatation isolate BMJ4. The structure demonstrates a unprecedented dimer mediated by Cys177 disulfide bond. The HIV viron harbours these new dimeric form CA proteins if a.a.177 is Cys, which may provides a unique opportunity to trap HIV-1 p24 structure at a novel shoulder-to-shoulder dimer architecture. The dimeric linkage may serve for generation of HIV capsid from known pentamer and hexamer. Based on these findings,we focus on the effect of Cys177 to modulate the propagation and infection ability of HIV viron or pseudo-virion using matation on HIV proviral plasmid. Furthmore, permutation of dimeric, pentameric and hexameric disulfide introduction may generate some HIV capsid morphy assemble native capsid architecture, which might elucide in deep assembly mechanism of HIV shell.Using our paramount anti-CA mAb, it is possible to identify some functional epitopes related to HIV capsid assembly. The structure of functional CA dimer, HIV capsid or in complex with mAb Fab would be sovled by X-ray crystollography or cryo-EM 3D reconstruction. The outcome in present study is expected to bring insight into HIV research based on CA strcture and aimed to therapeutic or vaccine design purpose.