miR-124的表观遗传启动子DNA甲基化参与hiv -1相关神经认知障碍的发病机制

IF 3.2 Q2 GENETICS & HEREDITY
Epigenetics Insights Pub Date : 2018-10-14 eCollection Date: 2018-01-01 DOI:10.1177/2516865718806904
Shilpa Buch, Palsamy Periyasamy, Minglei Guo
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引用次数: 4

摘要

尽管抗逆转录病毒联合治疗(cART)在控制病毒血症方面有疗效,但中枢神经系统(CNS)仍然存在病毒库。持续的低水平病毒复制导致早期病毒蛋白的积累,包括HIV-1转录反激活因子(HIV-1 Tat)蛋白。基于cART不影响HIV-1 Tat水平的前提,并且由于cART方案无法进入中枢神经系统,HIV-1 Tat介导的神经炎症被认为是HIV-1相关神经认知障碍(HAND)的潜在介质。然而,HAND的发病机制尚不清楚。因此,了解病毒蛋白(如HIV-1 Tat)激活小胶质细胞的表观遗传/分子机制至关重要。Periyasamy等人发表的这项研究为hiv -1- tat介导的miR-124启动子DNA甲基化在通过MECP2-STAT3信号轴调节小胶质细胞激活中的作用提供了新的机制见解。此外,作者还报道,小鼠原代小胶质细胞暴露于HIV-1显著增加了原代miR-124-1和原代miR-124-2启动子的DNA甲基化(原代miR-124-3没有变化),导致小鼠原代小胶质细胞中原代miR-124-1和原代miR-124-2以及成熟miR-124的表达下调。作者还研究了MECP2-STAT3信号在hiv -1- tat介导的小胶质细胞激活中的作用。基于这些新发现,很明显miR-124的失调参与了HAND的发病机制,miR-124的恢复可以作为一种辅助治疗来抑制与HAND相关的神经炎症。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Involvement of Epigenetic Promoter DNA Methylation of miR-124 in the Pathogenesis of HIV-1-Associated Neurocognitive Disorders.

Despite the efficacy of combination antiretroviral therapy (cART) in controlling viremia, the central nervous system (CNS) continues to harbor viral reservoirs. The persistence of low-level virus replication leads to the accumulation of early viral proteins, including HIV-1 Transactivator of transcription (HIV-1 Tat) protein. Based on the premise that cART does not impact levels of HIV-1 Tat, and since the CNS is inaccessible to the cART regimens, HIV-1-Tat-mediated neuroinflammation has been implicated as an underlying mediator of HIV-1-associated neurocognitive disorders (HAND). The mechanism(s) underlying the pathogenesis of HAND, however, remain less understood. Understanding the epigenetic/molecular mechanism(s) by which viral proteins such as HIV-1 Tat activate microglia is thus of paramount importance. The study published by Periyasamy et al provides new mechanistic insights into the role of HIV-1-Tat-mediated DNA methylation of miR-124 promoter in regulating microglial activation via the MECP2-STAT3 signaling axis. Furthermore, the authors have also reported that exposure of mouse primary microglial cells to HIV-1 Tat notably increased DNA methylation of primary miR-124-1 and primary miR-124-2 promoters (with no change in primary miR-124-3), resulting in turn to downregulated expression of both primary miR-124-1 and primary miR-124-2 as well as mature miR-124 in mouse primary microglial cells. The authors also examined the involvement of MECP2-STAT3 signaling in HIV-1-Tat-mediated microglial activation. Based on these novel findings, it is evident that dysregulation of miR-124 is involved in the pathogenesis of HAND and that restoration of miR-124 could serve as an adjunctive treatment for dampening neuroinflammation associated with HAND.

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来源期刊
Epigenetics Insights
Epigenetics Insights GENETICS & HEREDITY-
CiteScore
5.10
自引率
0.00%
发文量
10
审稿时长
8 weeks
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