由于艾滋病病毒（HIV）的高突变率和免疫逃逸等特征，疫苗是对付艾滋病的最有效手段。目前仍然没有成功的艾滋病疫苗，根本原因是目前所用的免疫原在体内不能诱导出高效广谱的中和抗体，这需要我们有更有效的免疫原设计。马传贫病毒（EIAV）与HIV同属慢病毒属，有相似的基因组结构和生活周期。我们已有的数据显示在EIAV疫苗株中，gp45（相当于HIV gp41）异于野生株的关键位点定向突变可影响包膜蛋白的稳定性和病毒的侵染能力，但具体的EIAV gp45疫苗化机制还需要进一步阐明。本研究希望借助于EIAV疫苗研制成功的经验，针对HIV的包膜蛋白gp41,借助于结构、生化和病毒侵染等技术，仔细地比较EIAV野生株和疫苗株gp45的异同点，寻找其疫苗化基础，并将发现移植到HIV上进行验证，力求找到基于HIV gp41的免疫原设计方法，为目前停滞不前的艾滋病疫苗研制提供新的思路。

Human Immunodeficiency Virus (HIV) is the etiological agent of Acquired Immune Deficiency Syndrome (AIDS). Once infected by HIV, the individuals can't clean up the virus and most of the individuals will lose the control to the virus eventually even with extensive theraputic intervention. An effort to develop a sterile vaccine against AIDS has been initiated from the beginning of HIV identification. While with 30 years passed, most of trials for vaccine development have failed due to the high mutation rate and effective immune evasion of the virus. The vaccine against EIAV, which is developed more than 30 years ago by Chinese scientists, have been used as the reference of HIV vaccine study based on the similar life cycles between two viruses. The glycoprotein gp45 in EIAV plays similar roles as gp41 in HIV by forming a hetero-dimer with glycoprotein gp90 (ortholog of HIV gp120) on surface of viral particles, mediating the membrane fusion during viral invasion. The high conservation on sequence and low extent of glycosylation make gp45/gp41 a good target for vaccine development to induce broad spectrum neutralizing antibodies. Actually, several identified antibodies against gp41 in HIV, such as 2F5, 4E10 and 10E8, have been proven to neutralize HIV with wide spectrum. By comparasion of gp45 of wild type and vaccine strains of EIAV, a critical point mutation is identified, which is highy relevant to the evolution status of EIAV during viral attenuation. From the crystal structure of EIAV gp45 we determined recently, this point mutation is found to be localized in a/d position in heptad repeat, where natural mutation rarely occures. Our biochemical analysis reveals this type of mutations alter the stability of gp45 and influence the membrane fusion induced by viral infection. In this project, by multiple techniques such as crystallography, circular dichroism, and dectection of viral infection, we wish to uncover the underlying mechanism of EIAV vaccine derived from gp45, especially the importance of point mutations in a/d position in heptad repeat. The corresponding finding will be employed in HIV gp41 and the consequence on HIV replication and attenuation will be quantitated. By refering to EIAV, we hope our study could shed new light on the current stagnation on HIV vaccine development.