The V2 loop of HIV gp120 delivers costimulatory signals to CD4+T cells through Integrin α4β7and promotes cellular activation and infection

• DOI: 10.1073/pnas.2011501117
• Publication Date: 2020-12-07T22:15:28Z
• Authors: Livia R. Goes; Alia Sajani; Aida Sivro; Ronke Olowojesiku; Jocelyn C. Ray; Ian Perrone; Jason Yolitz; Alexandre Girard; Louise Leyre; Constantinos Kurt...; Lynn Morris; Giacomo Gorini; Genoveffa Franchini; Rosemarie D. Mason; Mario Roederer; Saurabh Mehandru; Marcelo A. Soares; Claudia Cicala; Anthony S. Fauci; James Arthos
• Keywords: CD4-Positive T-Lymphocytes; Integrins; 0303 health sciences; Anti-HIV Agents; Antibodies, Monoclonal; HIV Infections; Tretinoin; HIV Envelope Protein gp120; Lymphocyte Activation; Antibodies, Neutralizing; 3. Good health; Epitopes; 03 medical and health sciences; Protein Domains; Host-Pathogen Interactions; Humans; Simian Immunodeficiency Virus; Cell Proliferation; Signal Transduction

SignificanceUnderstanding the early events in HIV transmission will aid in the development of an efficacious HIV vaccine. Productive infection requires that virions access metabolically activated CD4+T cells. These cells are, in general, limited in number, which contributes to inefficient viral transmission. This report describes a mechanism whereby the HIV gp120 envelope protein can deliver activating signals to CD4+T cells. This activity may increase both productive infection in mucosal tissues around the time of transmission and the formation of viral reservoirs. gp120 mediates activating signals by binding to integrin α4β7. Antibodies specific to the V2 domain of gp120 block this interaction and may contribute to the efficacy of an HIV vaccine.