HIV-1 Envelope Protein Binds to and Signals Through Integrin alpha4beta7, the Gut Mucosal Homing Receptor for Peripheral T Cells
Infection with human immunodeficiency virus 1 (HIV-1) results in the dissemination of virus to gut-associated lymphoid tissue. Subsequently, HIV-1 mediates massive depletion of gut CD4+ T cells, which contributes to HIV-1-induced immune dysfunction. The migration of lymphocytes to gut-associated lymphoid tissue is mediated by integrin alpha4beta7. We demonstrate here that the HIV-1 envelope protein gp120 bound to an activated form of alpha4beta7. This interaction was mediated by a tripeptide in the V2 loop of gp120, a peptide motif that mimics structures presented by the natural ligands of alpha4beta7. On CD4+ T cells, engagement of alpha4beta7 by gp120 resulted in rapid activation of LFA-1, the central integrin involved in the establishment of virological synapses, which facilitate efficient cell-to-cell spreading of HIV-1.
Cell Movement, cells, cultured, fibroblasts, flow cytometry, HIV, envelope protein, humans, integrins, intestinal mucosa, killer cells, natural, ligands, protein binding, signal transduction
Arthos, James; Cicala, Claudia; Martinelli, Elena; Macleod, Katilyn; Van Ryk, Donald; Wei, Danlan; Xiao, Zhen; Veenstra, Timothy D.; Conrad, Thomas P.; Lempicki, Richard A.; McLaughlin, Sherry; Pascuccio, Massimiliano; Gopaul, Ravindra; McNally, Jonathan; Cruz, Catherine C; Censoplano, Nina; Chung, Eva; Reitano, Kristin N.; Kottilil, Shyam; Goode, Diana J.; and Fauci, Anthony S., "HIV-1 Envelope Protein Binds to and Signals Through Integrin alpha4beta7, the Gut Mucosal Homing Receptor for Peripheral T Cells" (2008). Pharmaceutical Sciences Faculty Publications. 329.