Department of Anesthesiology, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany.
Heinrich Pette Institute, Leibniz Institute for Experimental Virology, 20251, Hamburg, Germany.
Semin Immunopathol. 2020 Apr;42(2):187-200. doi: 10.1007/s00281-020-00783-3. Epub 2020 Feb 11.
Human immunodeficiency virus 1 (HIV-1) replicates through the integration of its viral DNA into the genome of human immune target cells. Chronically infected individuals thus carry a genomic burden of virus-derived sequences that persists through antiretroviral therapy. This burden consists of a small fraction of intact, but transcriptionally silenced, i.e. latent, viral genomes and a dominant fraction of defective sequences. Remarkably, all viral-derived sequences are subject to interaction with host cellular physiology at various levels. In this review, we focus on epigenetic aspects of this interaction. We provide a comprehensive overview of how epigenetic mechanisms contribute to establishment and maintenance of HIV-1 gene repression during latency. We furthermore summarize findings indicating that HIV-1 infection leads to changes in the epigenome of target and bystander immune cells. Finally, we discuss how an improved understanding of epigenetic features and mechanisms involved in HIV-1 infection could be exploited for clinical use.
人类免疫缺陷病毒 1（HIV-1）通过将其病毒 DNA 整合到人类免疫靶细胞的基因组中进行复制。因此，慢性感染个体携带持续存在于抗逆转录病毒治疗中的病毒衍生序列的基因组负担。该负担由一小部分完整但转录沉默的，即潜伏的，病毒基因组和占主导地位的缺陷序列组成。值得注意的是，所有病毒衍生序列都受到与宿主细胞生理在各个层面的相互作用。在这篇综述中，我们重点介绍这种相互作用的表观遗传方面。我们全面概述了表观遗传机制如何有助于在潜伏期内建立和维持 HIV-1 基因抑制。此外，我们总结了表明 HIV-1 感染导致靶细胞和旁观者免疫细胞的表观基因组发生变化的发现。最后，我们讨论了如何利用对 HIV-1 感染中涉及的表观遗传特征和机制的深入了解来进行临床应用。
