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

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 α 4 β 7 (α 4 β 7 ), the gut mucosal homing receptor. We find that α 4 β 7 high CD4 + T cells are more susceptible to productive infection than are α 4 β 7 low-neg CD4 + T cells in part because this cellular subset is enriched with metabolically active CD4 + T cells. α 4 β 7 high CD4 + T cells are CCR5 high and CXCR4 low ; on these cells, α 4 β 7 appears in a complex with CD4. The specific affinity of gp120 for α 4 β 7 provides a mechanism for HIV-1 to target activated cells that are critical for efficient virus propagation and dissemination following sexual transmission.