Integrin α4β7 Expression Increases HIV Susceptibility in Activated Cervical CD4 + T Cells by an HIV Attachment-Independent Mechanism

Background: CD4 + T cells are crucial for the establishment and dissemination of HIV in mucosal tissues during acute infection. Studies indicate that integrin α4β7 + CD4 + T cells are preferentially infected by HIV in vitro and during acute SIV infection. The integrin α4β7 is thought to promote HIV capture by target cells; however, the role of integrin α4β7 in HIV transmission remains controversial. In this study, we characterized immune phenotypes of human cervical T cells and examined HIV preference in integrin α4β7 + CD4 + T cells. In vitro all-trans retinoic acid-differentiated peripheral CD4 + T cells (atRA-differentiated cells) were included as a comparison. Results: In both peripheral and cervical cells, the majority of HIV p24 + cells were activated CD4 + T cells expressing integrin α4β7. Among infected atRA-differentiated cells, the frequency of CCR5 expression was higher in HIV p24 + cells than in HIV p24-cells; no such difference was observed in cervical cells. Neither the cyclic hexapeptide CWLDVC nor a monoclonal antibody against integrin α4β7 blocked HIV attachment or gp120 binding to target cells regardless of the presence of CD4, indicating that integrin α4β7 did not facilitate HIV capture by target cells. Conclusions: Integrin α4β7 expression increases HIV susceptibility, but the mechanism is not through promoting HIV binding to target cells.