HIV-1 envelope protein binds to and signals through integrin α4β7, the gut mucosal homing receptor for peripheral T cells
Martinelli,Elena; Arthos,James; Cicala,Claudia; 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 P.; Cruz,Catherine C.; Censoplano,Nina; Chung,Eva; Reitano,Kristin N.; Kottilil,Shyamasundaran; Goode,Diana J.; Fauci,Anthony S.
Nature Immunology 9(3): 301-309
Publication date: 2008
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 α4β7. We demonstrate here that the HIV-1 envelope protein gp120 bound to an activated form of α4β7. 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 α4β7. On CD4+ T cells, engagement of α4β7 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.