HIV感染的表观遗传学修饰:研究进展与挑战

Recent advances and challenges regarding epigenetic modification in HIV infection

HIV在感染人体数日内能够潜伏并形成储存库,是艾滋病治疗的难点。表观遗传学专注于序列变异之外的基因表达调控,近年来各种表观遗传学修饰研究结果促进了深入认识HIV致病机理和艾滋病治疗策略。本文简要介绍了表观遗传学原理,总结目前报道的HIV感染后宿主发生的表观遗传学改变,特别是以DNA甲基化、组蛋白修饰、RNA修饰和非编码RNA为代表的表观遗传学机制如何参与病毒潜伏、储存库的建立过程,以及对艾滋病功能性治疗策略带来的启示与挑战,旨在有更多研究团队关注HIV感染人群的表观遗传学研究,根据表观遗传学原理开发更多艾滋病治疗药物,制定合理可行的功能性治疗方案。

The establishment and maintenance of latent cellular reservoirs of human immunodeficiency virus(HIV)within days after infection remains a major obstacle to achieving functional HIV cure.Epigenetics pertains to the regulation of gene expression through means beyond mutations in DNA sequences.Research on epigenetic modifications in recent decades has facilitated in-depth understanding of HIV pathogenesis and ongoing AIDS therapy strategies.This review briefly introduces principles of epigenetics,and summarizes current epigenetic findings observed during HIV infection,particularly regarding the roles of epigenetic mechanisms including DNA methylation,histone modification,RNA modification,and non-coding RNAs in the processes of viral latency and formation of reservoirs.In addition,the implications and challenges of these epigenetic regulatory mechanisms in functional AIDS cure strategies are discussed.This review is aimed at encouraging more research groups to focus on epigenetic studies in HIV-infected populations,to develop more therapeutic drugs based on epigenetics,and to propose more rational and feasible functional AIDS cure strategies.