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 α4β7 (α4β7), the gut mucosal homing receptor. We find that α4β7^high CD4⁺T cells are more susceptible to productive infection than are α4β7^low-neg CD4⁺ T cells in part because this cellular subset is enriched with metabolically active CD4⁺ T cells. α4β7^high CD4⁺ T cells are CCR5^high and CXCR4^low; 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.