HIV-1 Tat-Induced Astrocytic Extracellular Vesicle miR-7 Impairs Synaptic Architecture.,Journal of Neuroimmune Pharmacology

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HIV-1 Tat-Induced Astrocytic Extracellular Vesicle miR-7 Impairs Synaptic Architecture.
Journal of Neuroimmune Pharmacology ( IF 5.2 ) Pub Date : 2019-08-10 , DOI: 10.1007/s11481-019-09869-8
Guoku Hu ₁ , Fang Niu ₁ , Ke Liao ₁ , Palsamy Periyasamy ₁ , Susmita Sil ₁ , Jinxu Liu ₂ , Shashank M Dravid ₂ , Shilpa Buch ₁

Affiliation

Although combination antiretroviral therapy (cART) has improved the health of millions of those living with HIV-1 (Human Immunodeficiency Virus, Type 1), the penetration into the central nervous system (CNS) of many such therapies is limited, thereby resulting in residual neurocognitive impairment commonly referred to as NeuroHIV. Additionally, while cART has successfully suppressed peripheral viremia, cytotoxicity associated with the presence of viral Transactivator of transcription (Tat) protein in tissues such as the brain, remains a significant concern. Our previous study has demonstrated that both HIV-1 Tat as well as opiates such as morphine, can directly induce synaptic alterations via independent pathways. Herein, we demonstrate that exposure of astrocytes to HIV-1 protein Tat mediates the induction and release of extracellular vesicle (EV) microRNA-7 (miR-7) that is taken up by neurons, leading in turn, to downregulation of neuronal neuroligin 2 (NLGN2) and ultimately to synaptic alterations. More importantly, we report that these impairments could be reversed by pretreatment of neurons with a neurotrophic factor platelet-derived growth factor-CC (PDGF-CC).

中文翻译：

HIV-1 Tat 诱导的星形细胞胞外囊泡 miR-7 损害突触结构。

尽管联合抗逆转录病毒疗法 (cART) 改善了数百万 HIV-1（人类免疫缺陷病毒，1 型）感染者的健康，但许多此类疗法对中枢神经系统 (CNS) 的渗透有限，从而导致残留神经认知障碍通常称为 NeuroHIV。此外，虽然 cART 已成功抑制外周病毒血症，但与大脑等组织中存在病毒反式转录激活因子 (Tat) 蛋白相关的细胞毒性仍然是一个重大问题。我们之前的研究表明，HIV-1 Tat 以及吗啡等阿片类药物都可以通过独立的途径直接诱导突触改变。在此处，我们证明星形胶质细胞暴露于 HIV-1 蛋白 Tat 介导细胞外囊泡 (EV) microRNA-7 (miR-7) 的诱导和释放，这些细胞外囊泡 (EV) microRNA-7 (miR-7) 被神经元吸收，进而导致神经元神经配素 2 (NLGN2) 的下调) 并最终导致突触改变。更重要的是，我们报告说，这些损伤可以通过用神经营养因子血小板衍生生长因子-CC (PDGF-CC) 预处理神经元来逆转。

更新日期：2019-08-10

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