Population Council Research that makes a difference

Abstract

The integrin α4β7 forms a complex with cell-surface CD4 and defines a T-cell subset that is highly susceptible to infection by HIV-1 (PDF) (HTML) 
Martinelli,Elena; Cicala,Claudia; McNally,Jonathan P.; Goode,Diana J.; Gopaul,Ravindra; Hiatt,Joseph; Jelicic,Katija; Kottilil,Shyamasundaran; Macleod,Katilyn; O'Shea,Angeline; Patel,Nikita; Van Ryk,Donald; Wei,Danlan; Pascuccio,Massimiliano; Yi,Ling; McKinnon,Lyle; Izulla,Preson; Kimani,Joshua; Kaul,Rupert; Fauci,Anthony S.; Arthos,James
Proceedings of the National Academy of Science of the United States of America 106(49): 20877-20882
Publication date: 2009

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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 α4β7 (α4β7), the gut mucosal homing receptor. We find that α4β7high CD4+ T cells are more susceptible to productive infection than are α4β7low-neg CD4+ T cells in part because this cellular subset is enriched with metabolically active CD4+ T cells. α4β7high CD4+ T cells are CCR5high and CXCR4low; on these cells, α4β7 appears in a complex with CD4. The specific affinity of gp120 for α4β7 provides a mechanism for HIV-1 to target activated cells that are critical for efficient virus propagation and dissemination following sexual transmission.

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