Binding of LFA-1 (CD11a) to intercellular adhesion molecule 3 (ICAM-3; CD50) and ICAM-2 (CD102) triggers transmigration of human immunodeficiency virus type 1-infected monocytes through mucosal epithelial cells

Transmigration of human immunodeficiency virus (HIV)-infected mononuclear c ells through the genital mucosa is one of the possible mechanisms of sexual transmission of HIV. Here, we investigated the transmigration of cell-asso ciated R5-tropic HIV type I (HIV-1) through a tight monolayer of human epit helial cells in vitro. We show that this process is dependent on an initial interaction between alphaL beta2 integrin CD11a/CD18 on infected monocytic cells and intercellular adhesion molecule 2 (ICAM-2; CD102) and ICAM-3 (CD 50) on the apical membrane of epithelial cells. The CD50 and CD102 ligands were overexpressed on epithelial cells when the cells were activated by pro inflammatory cytokines in the cellular microenvironment. An accumulation of proviral DNA was found in the transmigrated cells, clearly reflecting the preferential transepithelial migration of HIV-1-infected cells under proinf lammatory conditions. Our observations provide new insights supporting the hypothesis that HIV-infected mononuclear cells contained in genital secreti ons from infected individuals may cross the epithelial genital mucosa of an exposed receptive sexual partner, particularly under inflammatory conditio ns of damaged genital tissue. Understanding the fundamental aspects of the initial HIV entry process during sexual transmission remains a critical ste p for preventing human infection and developing further vaccinal strategies and virucidal agents.