Pharmaceutical Sciences Faculty Publications

HIV-1 Envelope Protein Binds to and Signals Through Integrin alpha4beta7, the Gut Mucosal Homing Receptor for Peripheral T Cells

Document Type

Article

Publication Date

3-1-2008

Journal Title

Nature Immunology

ISSN

1529-2916

Volume

9

Issue

3

First Page

301

Last Page

309

DOI

10.1038/ni1566

PubMed ID

18264102

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 alpha4beta7. We demonstrate here that the HIV-1 envelope protein gp120 bound to an activated form of alpha4beta7. 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 alpha4beta7. On CD4+ T cells, engagement of alpha4beta7 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.

Keywords

Cell Movement, cells, cultured, fibroblasts, flow cytometry, HIV, envelope protein, humans, integrins, intestinal mucosa, killer cells, natural, ligands, protein binding, signal transduction

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