HIV-1在感染早期，病毒主要利用CCR5作为辅助受体；而到晚期，随着CD4细胞数的降低，病毒使用CXCR4作为辅助受体。病毒辅助受体转变的机制目前尚不完全清楚，但已知，在这一过程中，病毒的包膜糖蛋白gp120 V3区在参与gp120与辅助受体的结合中起关键作用。为了分析V3区某个或某几个氨基酸位点对病毒亲嗜性的作用。本课题组对B亚型V3区氨基酸序列根据嗜性不同进行了比较分析。研究结果显示，除了已经证实的第11和第25位置的氨基酸与病毒的嗜性相关外，V3区的22位氨基酸与病毒的嗜性及病人的疾病进展具有明显的相关性。为了进一步验证我们的假设，本项目拟通过对不同嗜性的V3区22位点进行互换，利用伪病毒感染体系检测病毒嗜性的变化。此外，通过X射线衍射技术构建包膜蛋白模型，以检测22位氨基酸的变化对蛋白结构的影响，探讨病毒的感染机制，并对今后研制B亚型HIV的中和抗体及疫苗开发具有一定的意义。

It has been shown that viruses binding to CCR5 are almost exclusively present during the early asymptomatic stage of the infection whereas CXCR4-binding viruses may emerge in later phases of the infection and are associated with a CD4+ T cell count decline. However the mechanism of coreceptor switching is still unclear. The third hypervariable region (V3) of the HIV-1 gp120 protein is an important determinant of coreceptor usage of the virus. To analyze amino acids of the V3 loop associated with co-receptor usage in HIV-1 subtype B infection. Bioinformatics approaches are used to compare the amino acid sequences and secondary structure of the V3 loop of CCR5-tropism virus and CXCR4-tropism virus in HIV-1 subtype B. Our study suggests that position11, 22 and 25 of V3 is significantly associated with viral tropism and disease progress in HIV-1 subtype B. To further validate our hypothesis, we will interchanged the positive 22 of different tropic V3 loop and constructed the pseudoviruses. The ability of pseudoviruses infecting target cell was judged by detecting luciferase report gene. The envelope protein modes was made by X-ray diffraction technique to detect the role of the position 22 amino acid changes on protein structure. Which is helpful to study the mechanism of HIV-1 invading target cell and subtype B HIV-neutralizing antibody and the vaccine.