Neuronal-derived extracellular vesicles are enriched in the brain and serum of HIV-1 transgenic rats
Neuronal-derived extracellular vesicles are enriched in the brain and serum of HIV-1 transgenic rats
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DOI：
10.1080/20013078.2019.1703249
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发表时间：
2020-01-01
影响因子：
16
通讯作者：
Buch, Shilpa
中科院分区：
文献类型：
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作者：
Dagur, Raghubendra Singh;Liao, Ke;Buch, Shilpa
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（达特）在组织如脑中持续存在。虽然HIV-1不感染神经元细胞，但它对病毒达特蛋白介导的毒性敏感，导致神经炎症，这是HIV相关神经认知障碍（HAND）的基础。鉴于细胞外囊泡（EV）在细胞内稳态和病理条件下的作用，我们试图研究脑中神经元来源的EV数量的变化-如细胞粘附分子L1（L1 CAM）的存在所定义的，并评估HIV-1转基因（HIV-1 Tg）大鼠外周循环中L1 CAM + EV的存在。本研究的主要目的是研究长期暴露于HIV-1病毒蛋白对脑中神经元EV释放及其在全身隔室中转移的影响。使用示差超离心从野生型和HIV-1 Tg大鼠分离脑和血清EV，并使用Optiprep梯度方法进一步纯化。使用免疫沉淀进一步富集神经元EV的亚群。目前的研究结果表明，在HIV-1 Tg大鼠的大脑和血清中，L1 CAM（+）神经元衍生的EV的存在增加。
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.