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

Authors

James Arthos
Claudia Cicala
Elena Martinelli
Katilyn Macleod
Donald Van Ryk
Danlan Wei
Zhen Xiao
Timothy D. Veenstra, Cedarville UniversityFollow
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. Goode
Anthony S. Fauci

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

Recommended Citation

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.; and Fauci, Anthony S., "HIV-1 Envelope Protein Binds to and Signals Through Integrin alpha4beta7, the Gut Mucosal Homing Receptor for Peripheral T Cells" (2008). Pharmaceutical Sciences Faculty Publications. 329.
https://digitalcommons.cedarville.edu/pharmaceutical_sciences_publications/329