Erasmus University Medical Center, Rotterdam, The Netherlands.
Erasmus University Medical Center, Rotterdam, The Netherlands.
Int Rev Cell Mol Biol. 2018;335:191-243. doi: 10.1016/bs.ircmb.2017.07.011. Epub 2017 Oct 12.
In this review, we cover transcription regulation of human immunodeficiency virus type 1 (HIV-1) gene expression, focusing on the invaluable contributions, made by HIV research over the years, toward the field of transcription. In this context, the HIV promoter can be considered to be a well-studied model promoter, which although a viral promoter, is subject to the same cellular regulatory mechanisms that modulate the transcriptional control of endogenous host cellular genes. The molecular control of HIV-1 transcription has been well studied and considerable knowledge toward development of alternative strategies for therapies aimed at eradicating both active but also latent HIV-1 has been obtained. Additionally, HIV-1 studies have provided insight into fundamental aspects of transcriptional regulation including transcriptional stochasticity, RNA polymerase II pausing, chromatin regulation of transcription, the role of the +1 nucleosome, the use of an RNA enhancer element, i.e., TAR, the discovery, and essential function of P-TEFb, and the super elongation complex in transcription elongation. These findings have been important not only in deciphering the mechanisms used by HIV-1 to regulate its gene expression and to establish and maintain HIV latency for therapeutic advancement, but were at the same time seminal in pushing the transcription field forward.
在这篇综述中,我们涵盖了人类免疫缺陷病毒 1 型(HIV-1)基因表达的转录调控,重点介绍了 HIV 研究多年来对转录领域的宝贵贡献。在这种情况下,可以认为 HIV 启动子是一个经过充分研究的模型启动子,尽管它是一种病毒启动子,但它受到相同的细胞调节机制的调节,这些机制调节内源性宿主细胞基因的转录控制。HIV-1 转录的分子控制已经得到了很好的研究,并且已经获得了针对旨在根除活跃和潜伏 HIV-1 的替代治疗策略的大量知识。此外,HIV-1 研究提供了对转录调控基本方面的深入了解,包括转录随机性、RNA 聚合酶 II 暂停、转录的染色质调节、+1 核小体的作用、RNA 增强子元件(即 TAR)的使用、P-TEFb 的发现和基本功能,以及转录延伸中的超级延伸复合物。这些发现不仅对于破译 HIV-1 用于调节其基因表达以及建立和维持 HIV 潜伏期以推进治疗的机制非常重要,同时对于推动转录领域的发展也具有重要意义。