Virion Incorporation Of Integrin Alpha 4 Beta 7 Facilitates Hiv-1 Infection And Intestinal Homing

The intestinal mucosa is a key anatomical site for HIV-1 replication and CD4(+)T cell depletion. Accordingly, in vivo treatment with an antibody to the gut-homing integrin alpha 4 beta 7 was shown to reduce viral transmission, delay disease progression, and induce persistent virus control in macaques challenged with simian immunodeficiency virus (SIV). We show that integrin alpha 4 beta 7 is efficiently incorporated into the envelope of HIV-1 virions. Incorporated alpha 4 beta 7 is functionally active as it binds mucosal addressin cell adhesion molecule-1 (MAdCAM-1), promoting HIV-1 capture by and infection of MAdCAM-expressing cells, which in turn mediate trans-infection of bystander cells. Functional alpha 4 beta 7 is present in circulating virions from HIV-infected patients and SIV-infected macaques, with peak levels during the early stages of infection. In vivo homing experiments documented selective and specific uptake of alpha 4 beta 7(+)HIV-1 virions by high endothelial venules in the intestinal mucosa. These results extend the paradigm of tissue homing to a retrovirus and are relevant for the pathogenesis, treatment, and prevention of HIV-1 infection.