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 alpha 4 beta 7(+) CD4(+) T cells are preferentially infected by HIV in vitro and during acute SIV infection. The integrin alpha 4 beta 7 is thought to promote HIV capture by target cells; however, the role of integrin alpha 4 beta 7 in HIV transmission remains controversial. In this study, we characterized immune phenotypes of human cervical T cells and examined HIV preference in integrin alpha 4 beta 7(+) 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 alpha 4 beta 7. 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 alpha 4 beta 7 blocked HIV attachment or gp120 binding to target cells regardless of the presence of CD4, indicating that integrin alpha 4 beta 7 did not facilitate HIV capture by target cells. Conclusions: Integrin alpha 4 beta 7 expression increases HIV susceptibility, but the mechanism is not through promoting HIV binding to target cells.