Abstract

Development of Circulating Extracellular Vesicles as Theranostic of HIV Neurodisease Progression

Andrea Raymond, Associate Professor, Herbert Wertheim College of Medicine, Florida International University

Exosomal extracellular vesicles(xEVs) released by cells are detected in bodily fluids(blood, generally used for intercellular communication. However, xEVs also deliver cellular proteins, modify gene expression, and modulate immune responses in recipient cells. HIV-infected cells release xEVs containing the HIV Negative factor (Nef). The role of these xEVs and Nef+ exosomal EVs(Nef-xEVs) in HIV neuropathogenesis is unknown. Despite successful anti-retroviral therapy(ART), some aviremic people with HIV (PWH) develop HIV-associated neurocognitive disorders(HAND) that make it challenging to think, perform basic tasks, or work. Here, we show that changes in serum-derived xEVs cargo correlated with fluctuations in neurocognitive status over time in PWHs on ART. PWHs that maintain the same neurocognitive status from weeks 16, 48, and 96 have lowered CD8 T-cell, reduced xEV quantify, and decreased Nef-xEVs. In contrast, PWHs with fluctuating neurocognitive impairment(NCI) ranging from no NCI, NCI-moderate, to NCI-high exhibited elevated CD8+ T-cells counts and elevated serum-derived xEV Nef. Proteomic analysis revealed that specific proteins such as nebulin and neurexin-2 were up-regulated only in PWHs with fluctuating NCI, suggesting a potential role of these proteins in NCI. Results from this identify xEVs/Nef-xEVs cargo as potential biomarkers of NCI status in aviremic PWHs on ART.