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

James Arthos, Claudia Cicala, Elena Martinelli, Katilyn Macleod, Donald Van Ryk, Danlan Wei, Zhen Xiao, Timothy D. Veenstra, Thomas P. Conrad, Richard A. Lempicki, Sherry McLaughlin, Massimiliano Pascuccio, Ravindra Gopaul, Jonathan McNally, Catherine C. Cruz, Nina Censoplano, Eva Chung, Kristin N. Reitano, Shyam Kottilil, Diana J. GoodeAnthony S. Fauci

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407 Scopus citations

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 alpha;4 β7. On CD4+ T cells, engagement of alpha;4 β7 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.

Original languageEnglish (US)
Pages (from-to)301-309
Number of pages9
JournalNature Immunology
Volume9
Issue number3
DOIs
StatePublished - Mar 1 2008

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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    Arthos, J., Cicala, C., Martinelli, E., Macleod, K., Van Ryk, D., Wei, D., Xiao, Z., Veenstra, T. D., Conrad, T. P., Lempicki, R. A., McLaughlin, S., Pascuccio, M., Gopaul, R., McNally, J., Cruz, C. C., Censoplano, N., Chung, E., Reitano, K. N., Kottilil, S., ... Fauci, A. S. (2008). HIV-1 envelope protein binds to and signals through integrin α4β7, the gut mucosal homing receptor for peripheral T cells. Nature Immunology, 9(3), 301-309. https://doi.org/10.1038/ni1566