Dochnal Sara A, Francois Alison K, Cliffe Anna R
Department of Microbiology, Immunology and Cancer Biology, University of Virginia, Charlottesville, VA 22903, USA.
Viruses. 2021 Jul 27;13(8):1470. doi: 10.3390/v13081470.
The Human Herpesviruses persist in the form of a latent infection in specialized cell types. During latency, the herpesvirus genomes associate with cellular histone proteins and the viral lytic genes assemble into transcriptionally repressive heterochromatin. Although there is divergence in the nature of heterochromatin on latent herpesvirus genomes, in general, the genomes assemble into forms of heterochromatin that can convert to euchromatin to permit gene expression and therefore reactivation. This reversible form of heterochromatin is known as facultative heterochromatin and is most commonly characterized by polycomb silencing. Polycomb silencing is prevalent on the cellular genome and plays a role in developmentally regulated and imprinted genes, as well as X chromosome inactivation. As herpesviruses initially enter the cell in an un-chromatinized state, they provide an optimal system to study how de novo facultative heterochromatin is targeted to regions of DNA and how it contributes to silencing. Here, we describe how polycomb-mediated silencing potentially assembles onto herpesvirus genomes, synergizing what is known about herpesvirus latency with facultative heterochromatin targeting to the cellular genome. A greater understanding of polycomb silencing of herpesviruses will inform on the mechanism of persistence and reactivation of these pathogenic human viruses and provide clues regarding how de novo facultative heterochromatin forms on the cellular genome.
人类疱疹病毒以潜伏感染的形式存在于特定细胞类型中。在潜伏期间，疱疹病毒基因组与细胞组蛋白结合，病毒裂解基因组装成转录抑制性异染色质。尽管潜伏疱疹病毒基因组上的异染色质性质存在差异，但总体而言，基因组组装成的异染色质形式可转化为常染色质以允许基因表达，从而实现重新激活。这种可逆的异染色质形式被称为兼性异染色质，最常见的特征是多梳蛋白介导的沉默。多梳蛋白介导的沉默在细胞基因组中普遍存在，在发育调控基因、印记基因以及X染色体失活中发挥作用。由于疱疹病毒最初以未染色质化的状态进入细胞，它们提供了一个理想的系统来研究从头开始的兼性异染色质如何靶向DNA区域以及它如何导致基因沉默。在这里，我们描述了多梳蛋白介导的沉默如何可能组装到疱疹病毒基因组上，将关于疱疹病毒潜伏的已知信息与靶向细胞基因组的兼性异染色质相结合。对疱疹病毒多梳蛋白介导的沉默有更深入的了解将有助于揭示这些致病性人类病毒的持续存在和重新激活机制，并为细胞基因组上从头开始的兼性异染色质如何形成提供线索。
