Campbell Mel, Yang Wan-Shan, Yeh Wayne W, Kao Chen-Hsuan, Chang Pei-Ching
UC Davis Cancer Center, University of California, Davis, Davis, CA, United States.
Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan.
Front Microbiol. 2020 May 19;11:850. doi: 10.3389/fmicb.2020.00850. eCollection 2020.
Kaposi's sarcoma-associated herpesvirus (KSHV) is an oncogenic -herpesvirus that infects humans and exhibits a biphasic life cycle consisting of latent and lytic phases. Following entry into host cells, the KSHV genome undergoes circularization and chromatinization into an extrachromosomal episome ultimately leading to the establishment of latency. The KSHV episome is organized into distinct chromatin domains marked by variations in repressive or activating epigenetic modifications, including DNA methylation, histone methylation, and histone acetylation. Thus, the development of KSHV latency is believed to be governed by epigenetic regulation. In the past decade, interrogation of the KSHV epitome by genome-wide approaches has revealed a complex epigenetic mark landscape across KSHV genome and has uncovered the important regulatory roles of epigenetic modifications in governing the development of KSHV latency. Here, we highlight many of the findings regarding the role of DNA methylation, histone modification, post-translational modification (PTM) of chromatin remodeling proteins, the contribution of long non-coding RNAs (lncRNAs) in regulating KSHV latency development, and the role of higher-order episomal chromatin architecture in the maintenance of latency and the latent-to-lytic switch.
卡波西肉瘤相关疱疹病毒（KSHV）是一种致癌性疱疹病毒，可感染人类，并呈现出由潜伏期和裂解期组成的双相生命周期。进入宿主细胞后，KSHV基因组会环化并染色质化形成一个染色体外附加体，最终导致潜伏期的建立。KSHV附加体被组织成不同的染色质结构域，这些结构域由抑制性或激活性表观遗传修饰的变化所标记，包括DNA甲基化、组蛋白甲基化和组蛋白乙酰化。因此，KSHV潜伏期的发展被认为受表观遗传调控。在过去十年中，通过全基因组方法对KSHV表位组的研究揭示了KSHV基因组中复杂的表观遗传标记景观，并揭示了表观遗传修饰在调控KSHV潜伏期发展中的重要调节作用。在这里，我们重点介绍了许多关于DNA甲基化、组蛋白修饰、染色质重塑蛋白的翻译后修饰（PTM）的作用、长链非编码RNA（lncRNA）在调节KSHV潜伏期发展中的贡献，以及高阶附加体染色质结构在维持潜伏期和潜伏-裂解转换中的作用的研究发现。
