爱泼斯坦-巴尔（EBV）是第一种人类致癌病毒，与许多淋巴增生性和恶性疾病密切相关，包括HL、BL、NPC和GC。EBV通过一种二相病毒生命周期来建立终生持续感染：潜伏期和溶解复制期。B细胞是EBV潜伏基因的关键区域，病毒基因表达在此处被抑制，促进病毒基因组的维持和免疫识别逃避。当EBV发生溶解性再活化时，病毒基因表达引发其复制、后代产生和传播。TSGs的表观遗传调控失调导致癌变。一些研究表明，EBV与异常的病毒DNA和宿主基因组甲基化模式相关，促进了免疫监测、识别逃避和宿主细胞持续感染。在其他表观遗传修饰中，DNA甲基化抑制了大部分病毒潜伏基因启动子，但留下了少数，并作为激活EBV溶解周期的先决条件，产生病毒后代。它通过重编程细胞为致癌、持久表型影响宿主表观基因组，这在一些恶性肿瘤中被证实。在其生命周期的每个阶段，EBV利用细胞表观遗传调控机制，暗示其独特的宿主-病原体关系。本综述总结了DNA甲基化对EBV相关启动子区域及病毒基因组的调控作用，以及在病理条件下的宿主基因组，重点介绍了EBV感染的潜伏、溶解和潜伏-溶解阶段涉及的病毒基因。此外，还提供了以甲基化为基础的EBV途径的示意图。版权所有 © 2023，由Elsevier B.V.出版。

Epstein Barr is the first-in-human oncogenic virus, closely related to numerous lymphoproliferative and malignant diseases, including HL, BL, NPC, and GC. EBV establishes life-long persistence infection portraying a biphasic viral life cycle: latent period and lytic replication. B-cells serve as critical regions for EBV latent genes, wherein viral gene expression is suppressed, promoting viral genome maintenance and immune recognition evasion. Upon its lytic reactivation, viral gene expression induces its replication, progeny production, and transmission. Dysregulations of epigenetic regulation in expressions of TSGs lead to carcinogenesis. Several studies reveal that EBV is associated with aberrant viral DNA and host genome methylation patterns, promoting immune monitoring, recognition evasiveness and host cell persistence. Among other epigenetic modifications, DNA methylation suppresses the majority of viral latent gene promoters, sparing a few, and acts as a prerequisite for activating EBV's lytic cycle, giving rise to viral progeny. It affects the host's epigenome via reprogramming cells to oncogenic, long-lasting phenotypes, as evident in several malignancies. At each phase of its life cycle, EBV exploits cellular mechanisms of epigenetic regulation, implying its unique host-pathogen relationship. This review summarized the DNA methylation's regulatory roles on several EBV-related promoter regions, along with the host genome in pathological conditions, highlights viral genes involved in a latent, lytic and latent-lytic phase of EBV infection. Moreover, it provides diagrammatic insights into methylation-based pathways in EBV.Copyright © 2023. Published by Elsevier B.V.