人类免疫缺陷病毒（HIV）导致的艾滋病是威胁人类健康的最严重的病毒传染性疾病，目前仍然缺乏有效的预防性疫苗和完全根治的药物。HIV外膜蛋白（Env）与CD4受体结合是HIV感染的第一个事件，Env蛋白高度变异，是HIV疫苗难以取得突破的重要原因之一；CD4作为HIV感染的第一受体，阻止CD4结合HIV或介导入胞可完全阻断HIV感染，CD4是人体内源性功能蛋白，具有高度的保守性，是良好的广谱抗病毒靶标，但需考虑干扰CD4是否影响其正常功能。我们前期研究获得与正在临床研究的CD4人源化单抗Ibalizumab表位不同的广谱中和抗体15A7，其表位位于CD4 D1结构域，具有广谱中和活性。本研究拟进一步筛选CD4抗体，解析CD4-15A7免疫复合物晶体结构，阐明抗病毒的分子机制，探索CD4抗体可能参与的信号通路，为靶向CD4的抗HIV感染研究提供结构信息和抗体、CD4受体、HIV三者的作用机制。

AIDS caused by Human Immunodeficient Virus (HIV) is the most sever viral infectious disease that poses great threat on human health. By far, there are no efficacious prophylactic vaccine and fully radical therapeutic drugs. HIV membrane protein (Env) binding with CD4 molecule initiates the virus infection. However, Env glycoprotein is undergoing highly genetic mutation, which leads to the failure of many vaccine clinical trials. CD4 is the primary receptor in HIV infection, thus the perturbation over HIV-CD4 binding or CD4-mediated cell entry will completely abrogate HIV infection. Moreover, CD4 is the innate molecule in human body with highly conservation in sequence and quaternary structure. So CD4 might be promising target for widely anti-HIV purpose, given the anti-CD4 activity not affect normal function in human body. In our previous work, we described a novel mAb that specifically binds human CD4 domain 1 blocking HIV-1 infection that is different from the humanized anti-CD4 antibody named Ibalizumab. In the present application, we will further screen more anti-CD4 antibody, solve the structure of CD4-15A7 immune complex by X-ray crystallography, and investigate the potential signal pathway induced by anti-CD binding. The results may shed light on the antiviral mechanism of various anti-CD4 antibodies, and provide useful structural information for antiviral drug design and understanding on the underlying relationship among antibody, CD4 and HIV.