Elucidating the role of extracellular vesicles microRNA cargo in HIV associated immune dysfunction

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Our project had two main specific aims: (1) to identify circulating miRNAs that are altered in HIV-infected individuals, and (2) to investigate whether altered miRNAs in extracellular vesicles from HIV patients regulate cytokine expression ex vivo. Over the past year of project implementation, we have collected three sets of plasma samples: from HIV-infected individuals before and after treatment, and from HIV-uninfected individuals. Using these samples, we have demonstrated a differential relative expression of miRNAs in plasma extracellular vesicles (EVs). Notably, our preliminary data suggest a trend of downregulation of EV miRNAs in the untreated HIV-infected group compared to the treated and HIV-uninfected groups. Our extended analysis further indicates that absolute levels of miRNA are lower in HIV-infected untreated individuals compared to treated and uninfected individuals. Additionally, we found that plasma miRNAs were more abundant compared to miRNAs in EVs but followed a similar trend to that of EVs. Given that absolute levels of miRNAs seem to be low in most individuals, we intend to first demonstrate the effect of EV miRNAs from HIV-infected individuals compared to those from HIV-uninfected individuals in vivo.