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

我们的项目有两个主要的具体目标：（1）鉴定HIV感染个体中改变的循环miRNA，以及（2）研究HIV患者细胞外囊泡中改变的miRNA是否调节离体细胞因子表达。在过去一年的项目实施中，我们收集了三组血浆样本：治疗前后的艾滋病毒感染者和未感染艾滋病毒的人。使用这些样品，我们已经证明了差异的相对表达的miRNA在血浆细胞外囊泡（EV）。值得注意的是，我们的初步数据表明，与治疗组和HIV未感染组相比，未治疗的HIV感染组中EV miRNA有下调的趋势。我们的扩展分析进一步表明，与治疗和未感染的个体相比，HIV感染的未治疗个体中miRNA的绝对水平较低。此外，我们发现，与EV中的miRNA相比，血浆miRNA更丰富，但遵循与EV相似的趋势。鉴于在大多数个体中miRNA的绝对水平似乎较低，我们打算首先证明来自HIV感染个体的EV miRNA与来自HIV未感染个体的EV miRNA相比在体内的作用。

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.