Virus-human chromatin interactions reorganise 3D genome and hijack KDM5B for promoting metastasis in nasopharyngeal carcinoma
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.
Authors
- Yhi Wong (ORCID: https://orcid.org/0000-0001-6852-0430)
- Ziyang Qi
- Larry Ka-Yue Chow (ORCID: https://orcid.org/0000-0001-7448-5811)
- Anne W.M. Lee (ORCID: https://orcid.org/0000-0003-2972-0231)
- Lanqi Gong (ORCID: https://orcid.org/0000-0002-1531-4948)
- Zhaozheng Hou (ORCID: https://orcid.org/0000-0001-8548-2798)
- Dittman Lai‐Shun Chung (ORCID: https://orcid.org/0000-0003-2425-8586)
- Wai Tong Ng (ORCID: https://orcid.org/0000-0001-6696-3000)
- Ying Wang (ORCID: https://orcid.org/0000-0003-2377-9101)
- Xin‐Yuan Guan (ORCID: https://orcid.org/0000-0002-4485-6017)
- Jiayan Liu (ORCID: https://orcid.org/0000-0003-2798-8795)
- Kiu-Wai Cheng (ORCID: https://orcid.org/0000-0002-8154-7395)
- Chi Man Tsang (ORCID: https://orcid.org/0000-0001-6817-4590)
- Kazi Anisha Islam (ORCID: https://orcid.org/0000-0001-5457-0648)
- Zhuoyou Yu
- Roger K.C. Ngan (ORCID: https://orcid.org/0000-0003-0755-3604)
- Yingpei Zhang
- Ping Feng (ORCID: https://orcid.org/0000-0002-2736-8345)
- Cyrus Paak-Ting Chak (ORCID: https://orcid.org/0009-0004-9162-9791)
- Zhonghua Liu (ORCID: https://orcid.org/0000-0003-3048-9823)
- Honglin Chen (ORCID: https://orcid.org/0000-0001-5108-8338)
- Wei Dai (ORCID: https://orcid.org/0000-0002-5558-0685)
- Victor Lee (ORCID: https://orcid.org/0000-0002-6283-978X)
- Songran Liu (ORCID: https://orcid.org/0000-0001-8770-7962)
- Zilu Huang
- Yunfei Xia
- Dora Lai‐Wan Kwong (ORCID: https://orcid.org/0000-0002-1304-2854)
Institutions
- Sun Yat-sen University (CN)
- Chinese University of Hong Kong (HK)
- Hong Kong Science and Technology Parks Corporation (HK)
- University of Hong Kong - Shenzhen Hospital (CN)
- Sun Yat-sen University Cancer Center (CN)
- Columbia University (US)
- University of Hong Kong (HK)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-08-04
- DOI
- https://doi.org/10.1038/s41467-025-61597-1
- Citations
- 2
- Primary Topic
- Viral-associated cancers and disorders
- Type
- article
- Field-Weighted Citation Impact
- 2.09
Funders
- Research Grants Council, University Grants Committee
- Innovation and Technology Commission
- University of Hong Kong
- Food and Health Bureau
- Guangdong Science and Technology Department
- Science, Technology and Innovation Commission of Shenzhen Municipality
- Hong Kong Government