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.
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.
Cicala
Claudia
C
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. ccicala@niaid.nih.gov
Martinelli
Elena
E
McNally
Jonathan P
JP
Goode
Diana J
DJ
Gopaul
Ravindra
R
Hiatt
Joseph
J
Jelicic
Katija
K
Kottilil
Shyamasundaran
S
Macleod
Katilyn
K
O'Shea
Angeline
A
Patel
Nikita
N
Van Ryk
Donald
D
Wei
Danlan
D
Pascuccio
Massimiliano
M
Yi
Ling
L
McKinnon
Lyle
L
Izulla
Preson
P
Kimani
Joshua
J
Kaul
Rupert
R
Fauci
Anthony S
AS
Arthos
James
J
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
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D016023:Integrins; D019713:Receptors, CCR5; C071777:integrin alpha4beta7