The V2 loop of HIV gp120 delivers costimulatory signals to CD4 T cells through Integrin αβ and promotes cellular activation and infection.

Acute HIV infection is characterized by rapid viral seeding of immunologic inductive sites in the gut followed by the severe depletion of gut CD4 T cells. Trafficking of αβ-expressing lymphocytes to the gut is mediated by MAdCAM, the natural ligand of αβ that is expressed on gut endothelial cells. MAdCAM signaling through αβ costimulates CD4 T cells and promotes HIV replication.

MAdCAM costimulation through Integrin-αβ promotes HIV replication.

Human gut-associated lymphoid tissues (GALT) play a key role in the acute phase of HIV infection. The propensity of HIV to replicate in these tissues, however, is not fully understood. Access and migration of naive and memory CD4 T cells to these sites is mediated by interactions between integrin αβ, expressed on CD4 T cells, and MAdCAM, expressed on high endothelial venules.