Poona College of Pharmacy, Department of Pharmaceutical Chemistry, Bharati Vidyapeeth (Deemed to be University), Erandwane, Pune 411038, Maharashtra, India.
Poona College of Pharmacy, Department of Pharmaceutical Chemistry, Bharati Vidyapeeth (Deemed to be University), Erandwane, Pune 411038, Maharashtra, India; UC Davis Comprehensive Cancer Center, Department of Entomology and Nematology, University of California Davis, One Shields Avenue, Davis, CA 95616, USA.
Biochim Biophys Acta Mol Basis Dis. 2023 Dec;1869(8):166838. doi: 10.1016/j.bbadis.2023.166838. Epub 2023 Aug 5.
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.
EB 病毒是首例人类致癌病毒，与多种淋巴组织增生性和恶性疾病密切相关，包括霍奇金淋巴瘤、弥漫性大 B 细胞淋巴瘤、鼻咽癌和胃癌。EB 病毒建立了终身持续性感染，表现出两相病毒生命周期：潜伏期和裂解复制。B 细胞是 EBV 潜伏基因的关键区域，其中病毒基因表达受到抑制，促进病毒基因组的维持和免疫识别逃逸。在其裂解再激活时，病毒基因表达诱导其复制、子代产生和传播。表观遗传调控失调导致 TSGs 的表达失调，从而导致癌变。几项研究表明，EB 病毒与异常的病毒 DNA 和宿主基因组甲基化模式有关，促进免疫监测、识别逃逸和宿主细胞持久性。在其他表观遗传修饰中，DNA 甲基化抑制大多数病毒潜伏基因启动子，仅保留少数启动子，并作为激活 EBV 裂解周期的先决条件，导致病毒子代产生。它通过将细胞重编程为致癌的、持久的表型来影响宿主的表观基因组，这在几种恶性肿瘤中显而易见。在其生命周期的每个阶段，EBV 都利用细胞的表观遗传调控机制，暗示其独特的宿主-病原体关系。本综述总结了 DNA 甲基化在几种 EBV 相关启动子区域以及宿主基因组在病理条件下的调节作用，强调了参与 EBV 感染潜伏、裂解和潜伏-裂解阶段的病毒基因。此外，它还提供了基于 EBV 甲基化途径的图示见解。
