학술논문
HIV-1 envelope protein binds to and signals through integrin α4 β7 , the gut mucosal homing receptor for peripheral T cells.
Document Type
Article
Author
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
Source
Subject
Language
ISSN
1529-2908
Abstract
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. [ABSTRACT FROM AUTHOR]