title: The integrin alpha4beta7 forms a complex with cell-surface CD4 and defines a T-cell subset that is highly susceptible to infection by HIV-1.
abstract: Both activated and resting CD4(+) T cells in mucosal tissues play important roles in the earliest phases of infection after sexual transmission of HIV-1, a process that is inefficient. HIV-1 gp120 binds to integrin alpha(4)beta(7) (alpha(4)beta(7)), the gut mucosal homing receptor. We find that alpha(4)beta(7)(high) CD4(+) T cells are more susceptible to productive infection than are alpha(4)beta(7)(low-neg) CD4(+) T cells in part because this cellular subset is enriched with metabolically active CD4(+) T cells. alpha(4)beta(7)(high) CD4(+) T cells are CCR5(high) and CXCR4(low); on these cells, alpha(4)beta(7) appears in a complex with CD4. The specific affinity of gp120 for alpha(4)beta(7) provides a mechanism for HIV-1 to target activated cells that are critical for efficient virus propagation and dissemination following sexual transmission.
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. ccicala@niaid.nih.gov
authors.forename: Claudia
authors.initials: C
authors.lastname: Cicala
authors.forename: Elena
authors.initials: E
authors.lastname: Martinelli
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: McNally
authors.forename: Diana J
authors.initials: DJ
authors.lastname: Goode
authors.forename: Ravindra
authors.initials: R
authors.lastname: Gopaul
authors.forename: Joseph
authors.initials: J
authors.lastname: Hiatt
authors.forename: Katija
authors.initials: K
authors.lastname: Jelicic
authors.forename: Shyamasundaran
authors.initials: S
authors.lastname: Kottilil
authors.forename: Katilyn
authors.initials: K
authors.lastname: Macleod
authors.forename: Angeline
authors.initials: A
authors.lastname: O'Shea
authors.forename: Nikita
authors.initials: N
authors.lastname: Patel
authors.forename: Donald
authors.initials: D
authors.lastname: Van Ryk
authors.forename: Danlan
authors.initials: D
authors.lastname: Wei
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Pascuccio
authors.forename: Ling
authors.initials: L
authors.lastname: Yi
authors.forename: Lyle
authors.initials: L
authors.lastname: McKinnon
authors.forename: Preson
authors.initials: P
authors.lastname: Izulla
authors.forename: Joshua
authors.initials: J
authors.lastname: Kimani
authors.forename: Rupert
authors.initials: R
authors.lastname: Kaul
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Fauci
authors.forename: James
authors.initials: J
authors.lastname: Arthos
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015704:CD4 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D002462:Cell Membrane / Q000187:drug effects / Q000276:immunology / Q000821:virology; D005260:Female; D005836:Genitalia, Female / Q000187:drug effects / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D006801:Humans; D047468:Immunoprecipitation; D016023:Integrins / Q000276:immunology*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D019713:Receptors, CCR5 / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000821:virology*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D016023:Integrins; D019713:Receptors, CCR5; C071777:integrin alpha4beta7