Epstein–Barr virus (EBV) is associated with several human malignancies including 8–10% of gastric cancers (GCs). Genome-wide analysis of 3D chromatin topologies across GC lines, primary tissue and normal gastric samples revealed chromatin domains specific to EBV-positive GC, exhibiting heterochromatin-to-euchromatin transitions and long-range human–viral interactions with non-integrated EBV episomes. EBV infection in vitro suffices to remodel chromatin topology and function at EBV-interacting host genomic loci, converting H3K9me3⁺ heterochromatin to H3K4me1⁺/H3K27ac⁺ bivalency and unleashing latent enhancers to engage and activate nearby GC-related genes (for example TGFBR2 and MZT1). Higher-order epigenotypes of EBV-positive GC thus signify a novel oncogenic paradigm whereby non-integrative viral genomes can directly alter host epigenetic landscapes (‘enhancer infestation’), facilitating proto-oncogene activation and tumorigenesis.

爱泼斯坦-巴尔病毒（EBV）与几种人类恶性肿瘤相关，包括8-10％的胃癌（GCs）。全基因组范围内跨GC系，原发组织和正常胃样品的3D染色质拓扑分析显示，EBV阳性GC特有的染色质结构域，表现出异染色质向正常染色质的转变以及与非整合EBV附加体的长期人-病毒相互作用。体外EBV感染足以重塑染色质拓扑结构并在与EBV相互作用的宿主基因组位点发挥功能，将H3K9me3 ⁺异染色质转化为H3K4me1 ⁺ / H3K27ac ⁺双价并释放潜在的增强子以接合和激活附近的GC相关基因（例如TGFBR2和MZT1）。因此，EBV阳性GC的高阶表型代表了一种新的致癌范例，其中非整合型病毒基因组可以直接改变宿主的表观遗传环境（“侵染性”），促进原癌基因的活化和肿瘤的发生。