整合素分子α4β7表达在淋巴细胞表面，其生理作用是介导淋巴细胞向肠相关淋巴组织的免疫效应部位归巢。艾滋病毒（HIV-1）包膜糖蛋白gp120可以与α4β7相互作用而增强病毒感染性，但目前对α4β7在HIV-1感染中所起的作用及机制仍不清楚。我们的前期研究表明：gp120上的α4β7作用位点对于维持病毒感染性非常重要；外周血淋巴细胞经激活表达α4β7后，朝gp120的迁移能力显著增强，迁移水平呈现依赖α4β7表达水平的个体差异。基于以上工作基础，本项目致力于研究gp120与α4β7相互作用介导的淋巴细胞定向迁移的机制；二者相互作用力的毒株差异及其与毒株传播适合度之间的关联；个体水平α4β7的表达差异及其与HIV-1易感性的相关性；以及在黏膜水平阻断gp120-α4β7相互作用对HIV-1复制的影响。本项目将深入了解α4β7在HIV-1致病过程中扮演的作用，有助于揭示HIV-1早期致病机制。

HIV-1 gp120 was reported to interact with α4β7, an integrin mediating the homing of lymphoids to gut-associated lymphoid tissue (GALT). However, the precise roles played by α4β7 in HIV-1 infection remains to be defined. Our preliminary results have showed that the α4β7-binding site on HIV-1 gp120 is of great importance in maintaining viral infectivity. We also found that the migration activity of retinoic acid (RA)-treated peripheral blood mononuclear cells (PBMC) toward gp120 was significantly higher than that of PBMC without RA treatment, although significance varied between donors. This proposed project aims to investigate the mechanism underlying gp120-directed α4β7+ PBMC migration, and to compare the binding affinity between α4β7 and gp120 of different early transmitted HIV-1 strains. We also intend to study the heterogeneity of α4β7 expression in different individuals and its correlation with HIV-1 acquisition, as well as the impact of blocking gp120-α4β7 interaction on HIV-1 infection of human mucosal tissues. The outcoming results would provide valuable information to understand the significance of α4β7 in HIV-1 pathogenesis, particularly during the early stages of HIV-1 transmission.