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Journal Club

  • Center for Virology and Vaccine Research 3 Blackfan Circle - 1033 Boston, MA, 02115 United States (map)

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 4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 47 is efficiently incorporated into the envelope of HIV-1 virions. Incorporated 4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 4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 4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.  (As published in Science Immunology Magazine, May 12th, 2017)