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

Dittman Lai-Shun Chung, Zhaozheng Hou, Ying Wang, Kazi Anisha Islam, Songran Liu, Jiayan Liu, Larry Ka-Yue Chow, Yuki Yuk-Wun Wong, Cyrus Paak-Ting Chak, Yingpei Zhang, Lanqi Gong, Ziyang Qi, Kiu-Wai Cheng, Zhuoyou Yu, Ping Feng, Zilu Huang, Roger Kai-Cheong Ngan, Xinyuan Guan, Wai-Tong Ng, Zhonghua Liu, Anna Chi-Man Tsang, Dora Lai-Wan Kwong, Anne Wing-Mui Lee, Victor Ho-Fun Lee, Honglin Chen, Yunfei Xia and Wei Dai ()
Additional contact information
Dittman Lai-Shun Chung: The University of Hong Kong
Zhaozheng Hou: The University of Hong Kong
Ying Wang: The Sun Yat-sen University Cancer Center
Kazi Anisha Islam: The University of Hong Kong
Songran Liu: The University of Hong Kong
Jiayan Liu: Hong Kong Science and Technology Park
Larry Ka-Yue Chow: The University of Hong Kong
Yuki Yuk-Wun Wong: The University of Hong Kong
Cyrus Paak-Ting Chak: The University of Hong Kong
Yingpei Zhang: The University of Hong Kong
Lanqi Gong: The University of Hong Kong
Ziyang Qi: The University of Hong Kong
Kiu-Wai Cheng: The University of Hong Kong
Zhuoyou Yu: The University of Hong Kong
Ping Feng: Sun Yat-sen University Cancer Centre
Zilu Huang: Sun Yat-sen University Cancer Centre
Roger Kai-Cheong Ngan: The University of Hong Kong
Xinyuan Guan: The University of Hong Kong
Wai-Tong Ng: The University of Hong Kong
Zhonghua Liu: Columbia University
Anna Chi-Man Tsang: The Chinese University of Hong Kong
Dora Lai-Wan Kwong: The University of Hong Kong
Anne Wing-Mui Lee: The University of Hong Kong
Victor Ho-Fun Lee: The University of Hong Kong
Honglin Chen: Hong Kong Science and Technology Park
Yunfei Xia: The Sun Yat-sen University Cancer Center
Wei Dai: The University of Hong Kong

Nature Communications, 2025, vol. 16, issue 1, 1-21

Abstract: Abstract 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.

Date: 2025
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DOI: 10.1038/s41467-025-61597-1

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