HIV-1 envelope protein binds to and signals through integrin alpha4beta7, the gut mucosal homing receptor for peripheral T cells.
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.
Arthos
James
J
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. jarthos@niaid.nih.gov
Cicala
Claudia
C
Martinelli
Elena
E
Macleod
Katilyn
K
Van Ryk
Donald
D
Wei
Danlan
D
Xiao
Zhen
Z
Veenstra
Timothy D
TD
Conrad
Thomas P
TP
Lempicki
Richard A
RA
McLaughlin
Sherry
S
Pascuccio
Massimiliano
M
Gopaul
Ravindra
R
McNally
Jonathan
J
Cruz
Catherine C
CC
Censoplano
Nina
N
Chung
Eva
E
Reitano
Kristin N
KN
Kottilil
Shyam
S
Goode
Diana J
DJ
Fauci
Anthony S
AS
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism / Q000821:virology; D005434:Flow Cytometry; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000276:immunology* / Q000821:virology; D007694:Killer Cells, Natural / Q000276:immunology; D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology
D015699:HIV Envelope Protein gp120; D016023:Integrins; D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1; C071777:integrin alpha4beta7