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

被引：439

作者：

Arthos, James ^{[1
]}

Cicala, Claudia ^{[1
]}

Martinelli, Elena ^{[2
]}

Macleod, Katilyn ^{[1
]}

Van Ryk, Donald ^{[1
]}

Wei, Danlan ^{[1
]}

Xiao, Zhen ^{[3
]}

Veenstra, Timothy D. ^{[3
]}

Conrad, Thomas P. ^{[3
]}

Lempicki, Richard A. ^{[4
]}

McLaughlin, Sherry ^{[5
]}

Pascuccio, Massimiliano ^{[1
]}

Gopaul, Ravindra ^{[1
]}

McNally, Jonathan ^{[1
]}

Cruz, Catherine C. ^{[1
]}

Censoplano, Nina ^{[1
]}

Chung, Eva ^{[1
]}

Reitano, Kristin N. ^{[1
]}

Kottilil, Shyam ^{[1
]}

Goode, Diana J. ^{[1
]}

Fauci, Anthony S. ^{[1
]}

机构：

[1] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA

[2] Univ Genoa, Ctr Excellence Biomed Res, Genoa, Italy

[3] Sci Applicat Int Corp, Lab Proteom & Analyt Technol, Frederick, MD 21702 USA

[4] Sci Applicat Int Corp, Lab Immunopathogenesis & Bioinformat, Frederick, MD 21702 USA

[5] Univ Washington, Sch Med, Dept Microbiol, Seattle, WA 98195 USA

来源：

NATURE IMMUNOLOGY | 2008年 / 9卷 / 03期

关键词：

D O I：

10.1038/ni1566

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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 alpha(4)beta(7). We demonstrate here that the HIV-1 envelope protein gp120 bound to an activated form of alpha(4)beta(7). 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)beta(7). On CD4(+) T cells, engagement of alpha(4)beta(7) 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.

引用

页码：301 / 309

页数：9

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