Article abstract
Nature Immunology 9, 301 - 309 (2008)
Published online: 10 February 2008 | doi:10.1038/ni1566
HIV-1 envelope protein binds to and signals through integrin 
4
7, the gut mucosal homing receptor for peripheral T cells
James Arthos1,6, Claudia Cicala1,6, Elena Martinelli1,2,6, Katilyn Macleod1, Donald Van Ryk1, Danlan Wei1, Zhen Xiao3, Timothy D Veenstra3, Thomas P Conrad3, Richard A Lempicki4, Sherry McLaughlin5, Massimiliano Pascuccio1, Ravindra Gopaul1, Jonathan McNally1, Catherine C Cruz1, Nina Censoplano1, Eva Chung1, Kristin N Reitano1, Shyam Kottilil1, Diana J Goode1 & Anthony S Fauci1
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 
4
7. We demonstrate here that the HIV-1 envelope protein gp120 bound to an activated form of 47. 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 47. On CD4+ T cells, engagement of 47 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.
- Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
- Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy.
- Laboratory of Proteomics and Analytical Technologies, Science Applications International Corporation, Frederick, Maryland 21702, USA.
- Laboratory of Immunopathogenesis and Bioinformatics, Science Applications International Corporation, Frederick, Maryland 21702, USA.
- Department of Microbiology, University of Washington School of Medicine, Seattle, Washington 98195, USA.
- These authors contributed equally to this work.
Correspondence to: James Arthos1,6 e-mail: jarthos@niaid.nih.gov
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