Po-Ting Liu of the Center for Virology and Vaccine Research will be presenting "Virion Incorporation of Integrin a4B7 Facilitates HIV-1 Infection and Intestinal Homing"
ABSTRACT: 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 47 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 47 is efficiently incorporated into the envelope of HIV-1 virions. Incorporated 47 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 47 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 47+ 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. (As published in Science Immunology Magazine, May 12th, 2017)