Effects of exosome on the activation of CD4+ T cells in rhesus macaques: a potential application for HIV latency reactivation

Exosomes are small extracellular vesicles (EVs), released by a wide variety of cell types, carry donor origin-proteins, cytokines, and nucleic acids, transport these cargos to adjacent or distant specific recipient cells, and thereby regulate gene expression and activation of target cells. In this study, we isolated and identified exosomes in rhesus macaques, and investigated their effects on cell tropism and activation, especially their potential to reactivate HIV latency. The results indicated that plasma-derived exosomes preferentially fuse to TCR-activated T cells and autologous parent cells. Importantly, the uptake of exosomes, derived from IL-2 stimulated CD4+ T cells, effectively promoted reactivation of resting CD4+ T-cell, as indicated by an increased viral transcription rate in these cells. These findings provide premise for the potential application of exosome in the reactivation of HIV latency, in combination its use as functional delivery vehicles with antiretroviral therapy (ART).