Epigenetics InsightsPub Date : 2018-10-14eCollection Date: 2018-01-01DOI: 10.1177/2516865718806904
Shilpa Buch, Palsamy Periyasamy, Minglei Guo
{"title":"Involvement of Epigenetic Promoter DNA Methylation of miR-124 in the Pathogenesis of HIV-1-Associated Neurocognitive Disorders.","authors":"Shilpa Buch, Palsamy Periyasamy, Minglei Guo","doi":"10.1177/2516865718806904","DOIUrl":"https://doi.org/10.1177/2516865718806904","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":"11 ","pages":"2516865718806904"},"PeriodicalIF":2.2,"publicationDate":"2018-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2516865718806904","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36674850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}