Extracellular ATP induces the rapid release of HIV-1 from virus containing compartments of human macrophages

Significance

A major obstacle to the eradication of HIV-1 by combination antiretroviral therapy (cART) is the formation of cellular reservoirs in CD4 + T lymphocytes (carrying latently integrated provirus) and tissue macrophages. Infected macrophages assemble new virions in subcellular vacuoles known as virus-containing compartments (VCC), hiding them from the immune system and, in part, from antiretroviral agents. Here we report that extracellular ATP is capable of inducing the rapid release of virions accumulated in VCC via interaction with the P2X7 receptor and without inducing cell death, whereas the antidepressant agent Imipramine blocks the release. Thus, our study identifies two “druggable” targets affecting the release of stored virions from infected human macrophages that could bear relevance for purging HIV-1 reservoirs in individuals receiving cART.