Beijing Key Laboratory of Pediatric Respiratory Infectious Diseases, Key Laboratory of Major Diseases in Children, Ministry of Education, National Clinical Research Center for Respiratory Diseases, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China.
Research Unit of Critical Infection in Children, Chinese Academy of Medical Sciences, Beijing, 2019RU016, China.
Appl Microbiol Biotechnol. 2022 Jun;106(12):4413-4426. doi: 10.1007/s00253-022-12029-3. Epub 2022 Jun 28.
Epstein-Barr virus (EBV) is an oncogenic virus that is closely associated with several malignant and lymphoproliferative diseases. Studies have shown that the typical characteristic of EBV-associated diseases is aberrant methylation of viral DNA and the host genome. EBV gene methylation helps EBV escape from immune monitoring and persist in host cells. EBV controls viral gene promoter methylation by hijacking host epigenetic machinery to regulate the expression of viral genes. EBV proteins also interact with host epigenetic regulatory factors to mediate the methylation of the host's important tumour suppressor gene promoters, thereby participating in the occurrence of tumorigenesis. Since epigenetic modifications, including DNA methylation, are reversible in nature, drugs that target DNA methylation can be developed for epigenetic therapy against EBV-associated tumours. Various methylation modes in the host and EBV genomes may also be of diagnostic and prognostic value. This review summarizes the regulatory roles of DNA methylation on the promotor of EBV gene and host genome in EBV-associated diseases, proposes the application prospect of DNA methylation in early clinical diagnosis and treatment, and provides insight into methylation-based strategies against EBV-associated diseases. KEY POINTS: • Methylation of both the host and EBV genomes plays an important role in EBV-associated diseases. • The functions of methylation of the host and EBV genomes in the occurrence and development of EBV-associated diseases are diverse. • Methylation may be a therapeutic target or biomarker in EBV-associated diseases.
EB 病毒（EBV）是一种致癌病毒，与多种恶性和淋巴增生性疾病密切相关。研究表明，EBV 相关疾病的典型特征是病毒 DNA 和宿主基因组的异常甲基化。EBV 基因甲基化有助于 EBV 逃避免疫监测并在宿主细胞中持续存在。EBV 通过劫持宿主表观遗传机制来控制病毒基因启动子甲基化，从而调节病毒基因的表达。EBV 蛋白还与宿主表观遗传调节因子相互作用，介导宿主重要肿瘤抑制基因启动子的甲基化，从而参与肿瘤发生。由于表观遗传修饰（包括 DNA 甲基化）在性质上是可逆的，因此可以开发针对 EBV 相关肿瘤的靶向 DNA 甲基化的药物进行表观遗传治疗。宿主和 EBV 基因组中的各种甲基化模式也可能具有诊断和预后价值。本综述总结了 DNA 甲基化对 EBV 基因和宿主基因组启动子在 EBV 相关疾病中的调控作用，提出了 DNA 甲基化在早期临床诊断和治疗中的应用前景，并探讨了基于甲基化的策略对抗 EBV 相关疾病的作用。关键要点：• 宿主和 EBV 基因组的甲基化在 EBV 相关疾病中发挥重要作用。• 宿主和 EBV 基因组甲基化在 EBV 相关疾病发生和发展中的功能多种多样。• 甲基化可能是 EBV 相关疾病的治疗靶点或生物标志物。
