HIV-1 envelope protein binds to and signals through integrin α4β7, the gut mucosal homing receptor for peripheral T cells

J Arthos, C Cicala, E Martinelli, K Macleod… - Nature …, 2008 - nature.com
J Arthos, C Cicala, E Martinelli, K Macleod, D Van Ryk, D Wei, Z Xiao, TD Veenstra
Nature immunology, 2008nature.com
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 …
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.
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