Journal Article

Virus-human chromatin interactions reorganise 3D genome and hijack KDM5B for promoting metastasis in nasopharyngeal carcinoma

Kwong, Dora Lai-Wan, Lee, Victor Ho-Fun, Ngan, Roger Kai-Cheong, Wang, Ying, Guan, Xinyuan, Ng, Wai-Tong, Yu, Zhuoyou, Liu, Songran, Chow, Larry Ka-Yue, Xia, Yunfei, Liu, Zhonghua, Lee, Anne Wing-Mui, Chen, Honglin, Qi, Ziyang, Cheng, Kiu-Wai, Hou, Zhaozheng, Chung, Dittman Lai-Shun, Chak, Cyrus Paak-Ting, Feng, Ping, Gong, Lanqi, Dai, Wei, Huang, Zilu, Liu, Jiayan, Islam, Kazi Anisha, Zhang, Yingpei, Tsang, Anna Chi-Man, Wong, Yuki Yuk-Wun

2025

Overview

Epstein–Barr virus, the first identified human DNA tumour virus, is detectable in more than 90% of nasopharyngeal carcinoma patients in endemic regions. The 3D chromosome conformation analysis reveals that virus‒host chromatin interactions induce the spatial reorganisation of loops and compartments, resulting in “enhancer infestation” and switch of “H3K27 bivalency” at EBV-interacting regions. Through this mechanism, EBV hijacks KDM5B, a gatekeeper of genome stability, and its binding targets, leading to aberrant activation of an EBVIR-enhancer-KDM5B signature. Cancer cells with this signature present increased MYC activation, DNA damage responses, and epigenetic plasticity of epithelial-immune dual features with metastatic potential. Our multicentre multiomics study confirms that this signature is the prerequisite for chromosome instability and can be utilised as a risk factor for distant metastasis. This study highlights a mechanism in which latent viral episomes can alter the host high-order epigenotype, promoting transcriptional rewiring and metastasis in NPC. Epstein–Barr virus - host chromatin interactions in nasopharyngeal carcinoma remain poorly understood. Here, the authors characterise the virus‒host chromatin interactions leading to genome reorganisation and identify a KDM5B-relevant signature associated with distant metastasis.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13 / 13/1 / 13/105 / 13/51 / 14/32 / 38 / 38/15 / 38/39 / 38/91 / 42/47 / 45 / 45/23 / 631/67/322 / 692/4028/67/1536 / 692/4028/67/1858 / 96 / Cancer / Cell cycle / Cell Line, Tumor / Chromatin / Chromatin - genetics / Chromatin - metabolism / Chromosomes / Conformation / Deoxyribonucleic acid / DNA / DNA damage / DNA viruses / Epigenesis, Genetic / Epigenetics / Epstein-Barr virus / Epstein-Barr Virus Infections - genetics / Epstein-Barr Virus Infections - virology / Gene Expression Regulation, Neoplastic / Genome, Human / Genomes / Herpesvirus 4, Human - genetics / Herpesvirus 4, Human - physiology / Host-Pathogen Interactions - genetics / Humanities and Social Sciences / Humans / Infections / Jumonji Domain-Containing Histone Demethylases - genetics / Jumonji Domain-Containing Histone Demethylases - metabolism / Metastases / multidisciplinary / Myc protein / Nasopharyngeal carcinoma / Nasopharyngeal Carcinoma - genetics / Nasopharyngeal Carcinoma - metabolism / Nasopharyngeal Carcinoma - pathology / Nasopharyngeal Carcinoma - virology / Nasopharyngeal Neoplasms - genetics / Nasopharyngeal Neoplasms - metabolism / Nasopharyngeal Neoplasms - pathology / Nasopharyngeal Neoplasms - virology / Neoplasm Metastasis / Nuclear Proteins / Repressor Proteins - genetics / Repressor Proteins - metabolism / Risk factors / Science / Science (multidisciplinary) / Viruses