Turner Anne-Marie W, Margolis David M
UNC HIV Cure Center, University of North Carolina at Chapel Hill, Chapel Hill, NC.
Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC.
Yale J Biol Med. 2017 Jun 23;90(2):229-243. eCollection 2017 Jun.
The formation of a latent reservoir of Human Immunodeficiency Virus (HIV) infection hidden from immune clearance remains a significant obstacle to approaches to eradicate HIV infection. Towards an understanding of the mechanisms of HIV persistence, there is a growing body of work implicating epigenetic regulation of chromatin in establishment and maintenance of this latent reservoir. Here we discuss recent advances in the field of chromatin regulation, specifically in our understanding of the histone code, and how these discoveries relate to our current knowledge of the chromatin mechanisms linked to HIV transcriptional repression and the reversal of latency. We also examine mechanisms unexplored in the context of HIV latency and briefly discuss current therapies aimed at the induction of proviral expression within latently infected cells. We aim to emphasize that a greater understanding of the epigenetic mechanisms which govern HIV latency could lead to new therapeutic targets for latency reversal and clearance cure strategies.
形成一个隐藏于免疫清除之外的人类免疫缺陷病毒(HIV)潜伏感染库仍然是根除HIV感染方法的重大障碍。为了理解HIV持续存在的机制,越来越多的研究工作表明染色质的表观遗传调控参与了这个潜伏感染库的建立和维持。在这里,我们讨论染色质调控领域的最新进展,特别是我们对组蛋白密码的理解,以及这些发现如何与我们目前对与HIV转录抑制和潜伏期逆转相关的染色质机制的认识相关。我们还研究了在HIV潜伏期背景下尚未探索的机制,并简要讨论了目前旨在诱导潜伏感染细胞中前病毒表达的疗法。我们旨在强调,更深入地了解控制HIV潜伏期的表观遗传机制可能会为潜伏期逆转和清除治愈策略带来新的治疗靶点。