title: HIV-1 envelope protein binds to and signals through integrin alpha4beta7, 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 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.
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. jarthos@niaid.nih.gov
authors.forename: James
authors.initials: J
authors.lastname: Arthos
authors.forename: Claudia
authors.initials: C
authors.lastname: Cicala
authors.forename: Elena
authors.initials: E
authors.lastname: Martinelli
authors.forename: Katilyn
authors.initials: K
authors.lastname: Macleod
authors.forename: Donald
authors.initials: D
authors.lastname: Van Ryk
authors.forename: Danlan
authors.initials: D
authors.lastname: Wei
authors.forename: Zhen
authors.initials: Z
authors.lastname: Xiao
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Veenstra
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Conrad
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lempicki
authors.forename: Sherry
authors.initials: S
authors.lastname: McLaughlin
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Pascuccio
authors.forename: Ravindra
authors.initials: R
authors.lastname: Gopaul
authors.forename: Jonathan
authors.initials: J
authors.lastname: McNally
authors.forename: Catherine C
authors.initials: CC
authors.lastname: Cruz
authors.forename: Nina
authors.initials: N
authors.lastname: Censoplano
authors.forename: Eva
authors.initials: E
authors.lastname: Chung
authors.forename: Kristin N
authors.initials: KN
authors.lastname: Reitano
authors.forename: Shyam
authors.initials: S
authors.lastname: Kottilil
authors.forename: Diana J
authors.initials: DJ
authors.lastname: Goode
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Fauci
mesh_terms: 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
chemical_list: D015699:HIV Envelope Protein gp120; D016023:Integrins; D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1; C071777:integrin alpha4beta7