The V2 loop of HIV gp120 delivers costimulatory signals to CD4 ⁺ T cells through Integrin α ₄ β ₇ and promotes cellular activation and infection

Significance Understanding the early events in HIV transmission will aid in the development of an efficacious HIV vaccine. Productive infection requires that virions access metabolically activated CD4 + T cells. These cells are, in general, limited in number, which contributes to inefficient viral transmission. This report describes a mechanism whereby the HIV gp120 envelope protein can deliver activating signals to CD4 + T cells. This activity may increase both productive infection in mucosal tissues around the time of transmission and the formation of viral reservoirs. gp120 mediates activating signals by binding to integrin α 4 β 7 . Antibodies specific to the V2 domain of gp120 block this interaction and may contribute to the efficacy of an HIV vaccine.