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

Research output: Contribution to journalArticle

395 Citations (Scopus)

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

Fingerprint

Human Immunodeficiency Virus env Gene Products
Lymphocyte Homing Receptors
Integrins
HIV-1
Lymphoid Tissue
T-Lymphocytes
Lymphocyte Function-Associated Antigen-1
Synapses
Lymphocytes
Ligands
Viruses
Peptides
Infection

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Arthos, J., Cicala, C., Martinelli, E., Macleod, K., Van Ryk, D., Wei, D., ... 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
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. ; Fauci, Anthony S. / HIV-1 envelope protein binds to and signals through integrin α4β7, the gut mucosal homing receptor for peripheral T cells. In: Nature Immunology. 2008 ; Vol. 9, No. 3. pp. 301-309.
@article{82040c44a5e745a99013dfc9a1d76024,
title = "HIV-1 envelope protein binds to and signals through integrin α4β7, the gut mucosal homing receptor for peripheral T cells",
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.",
author = "James Arthos and Claudia Cicala and Elena Martinelli and Katilyn Macleod and {Van Ryk}, Donald and Danlan Wei and Zhen Xiao and Veenstra, {Timothy D.} and Conrad, {Thomas P.} and Lempicki, {Richard A.} and Sherry McLaughlin and Massimiliano Pascuccio and Ravindra Gopaul and Jonathan McNally and Cruz, {Catherine C.} and Nina Censoplano and Eva Chung and Reitano, {Kristin N.} and Shyam Kottilil and Goode, {Diana J.} and Fauci, {Anthony S.}",
year = "2008",
month = "3",
day = "1",
doi = "10.1038/ni1566",
language = "English (US)",
volume = "9",
pages = "301--309",
journal = "Nature Immunology",
issn = "1529-2908",
publisher = "Nature Publishing Group",
number = "3",

}

Arthos, J, Cicala, C, Martinelli, E, Macleod, K, Van Ryk, D, Wei, D, Xiao, Z, Veenstra, TD, Conrad, TP, Lempicki, RA, McLaughlin, S, Pascuccio, M, Gopaul, R, McNally, J, Cruz, CC, Censoplano, N, Chung, E, Reitano, KN, Kottilil, S, Goode, DJ & Fauci, AS 2008, 'HIV-1 envelope protein binds to and signals through integrin α4β7, the gut mucosal homing receptor for peripheral T cells', Nature Immunology, vol. 9, no. 3, pp. 301-309. https://doi.org/10.1038/ni1566

HIV-1 envelope protein binds to and signals through integrin α4β7, the gut mucosal homing receptor for peripheral T cells. / 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.; Fauci, Anthony S.

In: Nature Immunology, Vol. 9, No. 3, 01.03.2008, p. 301-309.

Research output: Contribution to journalArticle

TY - JOUR

T1 - HIV-1 envelope protein binds to and signals through integrin α4β7, the gut mucosal homing receptor for peripheral T cells

AU - Arthos, James

AU - Cicala, Claudia

AU - Martinelli, Elena

AU - Macleod, Katilyn

AU - Van Ryk, Donald

AU - Wei, Danlan

AU - Xiao, Zhen

AU - Veenstra, Timothy D.

AU - Conrad, Thomas P.

AU - Lempicki, Richard A.

AU - McLaughlin, Sherry

AU - Pascuccio, Massimiliano

AU - Gopaul, Ravindra

AU - McNally, Jonathan

AU - Cruz, Catherine C.

AU - Censoplano, Nina

AU - Chung, Eva

AU - Reitano, Kristin N.

AU - Kottilil, Shyam

AU - Goode, Diana J.

AU - Fauci, Anthony S.

PY - 2008/3/1

Y1 - 2008/3/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=39449098115&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=39449098115&partnerID=8YFLogxK

U2 - 10.1038/ni1566

DO - 10.1038/ni1566

M3 - Article

C2 - 18264102

AN - SCOPUS:39449098115

VL - 9

SP - 301

EP - 309

JO - Nature Immunology

JF - Nature Immunology

SN - 1529-2908

IS - 3

ER -