EB 病毒 (EBV) 与多种类型的人类癌症有关，据报道 DNA 甲基化的变化有助于病毒驱动的致癌作用，特别是在上皮来源的癌症中。在之前的一项研究中，我们证明 EBV 感染人原代结肠细胞 (HCoEpC) 并在这些细胞内复制，从而产生促炎和促肿瘤作用。值得注意的是，这些影响主要是通过用 PAA 抑制病毒复制来预防的。有趣的是，EBV 诱导的效应与 DNMT1 的上调相关，并且可以通过用 5-AZA 预处理细胞来抵消，这表明 DNA 高甲基化的作用。在此背景下，当前的研究调查了 HCoEpC 中 EBV 感染诱导的甲基化变化，无论是否存在 PAA、或 ERK1/2 和 STAT3 抑制剂，已知 EBV 激活并参与甲基化失调的途径在肿瘤细胞中。本研究中进行的全基因组甲基化分析使我们能够识别受这些表观遗传变化影响的几个生物过程和基因，从而深入了解导致 EBV 诱导病理效应的可能潜在机制。具体来说，我们发现该病毒诱导了显着的甲基化变化，其中高甲基化比低甲基化更普遍。涉及胚胎发生、癌变和炎症的多个基因受到影响。版权所有 © 2024。由 Elsevier B.V. 出版。

Epstein-Barr Virus (EBV) is associated with several types of human cancers, and changes in DNA methylation are reported to contribute to viral-driven carcinogenesis, particularly in cancers of epithelial origin. In a previous study, we demonstrated that EBV infects human primary colonic cells (HCoEpC) and replicates within these cells, leading to pro-inflammatory and pro-tumorigenic effects. Notably, these effects were mostly prevented by inhibiting viral replication with PAA. Interestingly, the EBV-induced effects correlated with the upregulation of DNMT1 and were counteracted by pretreating cells with 5-AZA, suggesting a role for DNA hypermethylation. Building on this background, the current study investigates the methylation changes induced by EBV infection in HCoEpC, both in the presence and absence of PAA, or ERK1/2 and STAT3 inhibitors, pathways known to be activated by EBV and involved in the dysregulation of methylation in tumor cells. The genome-wide methylation analysis conducted in this study allowed us to identify several biological processes and genes affected by these epigenetic changes, providing insights into the possible underlying mechanisms leading to the pathological effects induced by EBV. Specifically, we found that the virus induced significant methylation changes, with hypermethylation being more prevalent than hypomethylation. Several genes involved in embryogenesis, carcinogenesis, and inflammation were affected.Copyright © 2024. Published by Elsevier B.V.