Macrophages are a relevant target of HIV-1 infection and a peculiar viral reservoir in individuals receiving cART because of their capacity to actively generate and store new progeny virions in intracellular vacuolar compartments of debated origin. Therefore, we investigated the functional nature of this intracellular compartment in terms of its responsiveness to stimuli, such as ATP, capable of modulating the release of cytokines in human primary monocyte-derived macrophage (MDM) of HIV seronegative donors. MDM were infected either with a replication-competent R5 HIV-1 strain or with a VSVg-pseudotyped vector expressing eGFP. In addition, the U937-derived promonocytic cell line U1, chronically infected with HIV-1, was differentiated to macrophage-like cells and then exposed to ATP to induce virion release, as assessed by RT activity and by other visual methods. Indeed, short course (10–30 minutes) stimulation with extracellular ATP induced virion release from both HIV-infected MDM and PMA-differentiated U1 cells with a concomitant reduction of intracellular virions. Pharmacological inhibitors of the microvescicle release pathway prevented HIV virion release, suggesting that this may represent a potentially “druggable” target for identifying novel strategies of purging tissue resident infected macrophages in individuals under cART.
© 2014 by Lippincott Williams & Wilkins