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Neuronal-derived extracellular vesicles are enriched in the brain and serum of HIV-1 transgenic rats.
Journal of Extracellular Vesicles ( IF 16.0 ) Pub Date : 2019-12-20 , DOI: 10.1080/20013078.2019.1703249
Raghubendra Singh Dagur 1 , Ke Liao 1 , Susmita Sil 1 , Fang Niu 1 , Zhiqiang Sun 2 , Yuri L Lyubchenko 2 , Eric S Peeples 3 , Guoku Hu 1 , Shilpa Buch 1
Affiliation  

Despite the efficacy of combination antiretroviral therapy (ART) in controlling human immunodeficiency virus (HIV-1) replication, cytotoxic viral proteins such as HIV-1 transactivator of transcription (Tat) persist in tissues such as the brain. Although HIV-1 does not infect neuronal cells, it is susceptible to viral Tat protein-mediated toxicity, leading to neuroinflammation that underlies HIV-associated neurocognitive disorders (HAND). Given the role of extracellular vesicles (EVs) in both cellular homoeostasis and under pathological conditions, we sought to investigate the alterations in the quantity of neuronal-derived EVs in the brain - as defined by the presence of cell adhesion molecule L1 (L1CAM) and to evaluate the presence of L1CAM+ EVs in the peripheral circulation of HIV-1 transgenic (HIV-1 Tg) rats. The primary goal of this study was to investigate the effect of long-term exposure of HIV-1 viral proteins on the release of neuronal EVs in the brain and their transfer in the systemic compartment. Brain and serum EVs were isolated from both wild type and HIV-1 Tg rats using differential ultracentrifugation with further purification using the Optiprep gradient method. The subpopulation of neuronal EVs was further enriched using immunoprecipitation. The current findings demonstrated increased presence of L1CAM+ neuronal-derived EVs both in the brain and serum of HIV-1 Tg rats.

中文翻译:

神经元衍生的细胞外囊泡在HIV-1转基因大鼠的大脑和血清中富集。

尽管联合抗逆转录病毒疗法(ART)在控制人类免疫缺陷病毒(HIV-1)复制方面具有功效,但细胞毒性病毒蛋白(如HIV-1转录反式激活因子(Tat))仍存在于组织(如大脑)中。尽管HIV-1不会感染神经元细胞,但它很容易受到病毒Tat蛋白介导的毒性的影响,导致以HIV相关的神经认知障碍(HAND)为基础的神经炎症。考虑到细胞外囊泡(EVs)在细胞稳态和病理状态下的作用,我们试图研究脑中神经元衍生EV数量的变化-定义为存在细胞粘附分子L1(L1CAM)和评估L-1CAM + EVs在HIV-1转基因(HIV-1 Tg)大鼠的外周循环中的存在。这项研究的主要目的是研究长期暴露HIV-1病毒蛋白对大脑中神经元EV的释放以及它们在体腔中的转移的影响。使用差异超速离心从野生型和HIV-1 Tg大鼠中分离脑和血清EV,并使用Optiprep梯度法进一步纯化。使用免疫沉淀进一步丰富了神经元电动车的亚群。目前的发现表明,HIV-1 Tg大鼠的大脑和血清中L1CAM +神经元衍生的EV的存在增加。使用差异超速离心从野生型和HIV-1 Tg大鼠中分离脑和血清EV,并使用Optiprep梯度法进一步纯化。使用免疫沉淀进一步丰富了神经元电动车的亚群。目前的发现表明,HIV-1 Tg大鼠的大脑和血清中L1CAM +神经元衍生的EV的存在增加。使用差异超速离心从野生型和HIV-1 Tg大鼠中分离脑和血清EV,并使用Optiprep梯度法进一步纯化。使用免疫沉淀进一步丰富了神经元电动车的亚群。目前的发现表明,HIV-1 Tg大鼠的大脑和血清中L1CAM +神经元衍生的EV的存在增加。
更新日期:2020-04-20
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