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通过表观遗传学靶向治疗控制病毒感染。

Control of viral infections by epigenetic-targeted therapy.

机构信息

Department Pathogens & Inflammation-EPILAB, UPRES EA4266, University of Franche-Comté, University of Bourgogne Franche-Comté, 16 route de Gray, F-25030, Besançon cedex, France.

Université Libanaise, Beirut, Lebanon.

出版信息

Clin Epigenetics. 2019 Mar 27;11(1):55. doi: 10.1186/s13148-019-0654-9.

Abstract

Epigenetics is defined as the science that studies the modifications of gene expression that are not owed to mutations or changes in the genetic sequence. Recently, strong evidences are pinpointing toward a solid interplay between such epigenetic alterations and the outcome of human cytomegalovirus (HCMV) infection. Guided by the previous possibly promising experimental trials of human immunodeficiency virus (HIV) epigenetic reprogramming, the latter is paving the road toward two major approaches to control viral gene expression or latency. Reactivating HCMV from the latent phase ("shock and kill" paradigm) or alternatively repressing the virus lytic and reactivation phases ("block and lock" paradigm) by epigenetic-targeted therapy represent encouraging options to overcome latency and viral shedding or otherwise replication and infectivity, which could lead eventually to control the infection and its complications. Not limited to HIV and HCMV, this concept is similarly studied in the context of hepatitis B and C virus, herpes simplex virus, and Epstein-Barr virus. Therefore, epigenetic manipulations stand as a pioneering research area in modern biology and could constitute a curative methodology by potentially consenting the development of broad-spectrum antivirals to control viral infections in vivo.

摘要

表观遗传学是研究基因表达修饰的科学,这些修饰不是由于基因突变或遗传序列变化引起的。最近,强有力的证据表明,这种表观遗传改变与人类巨细胞病毒(HCMV)感染的结果之间存在着紧密的相互作用。受人类免疫缺陷病毒(HIV)表观遗传重编程先前可能有希望的实验试验的指导,后者正在为控制病毒基因表达或潜伏期的两种主要方法铺平道路。通过表观遗传靶向治疗使 HCMV 从潜伏阶段重新激活(“冲击和杀伤”范式),或者通过抑制病毒裂解和再激活阶段(“阻断和锁定”范式)来抑制病毒,这是克服潜伏和病毒脱落或复制和感染力的令人鼓舞的选择,这最终可能导致控制感染及其并发症。这一概念不仅限于 HIV 和 HCMV,也在乙型肝炎和丙型肝炎病毒、单纯疱疹病毒和 EBV 等病毒的背景下进行了研究。因此,表观遗传学操纵是现代生物学中的一个开创性研究领域,通过潜在地同意开发广谱抗病毒药物来控制体内病毒感染,它可能构成一种治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77d8/6437953/352563d9f26a/13148_2019_654_Fig1_HTML.jpg

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