EB病毒株与宿主HLA相互作用驱动鼻咽癌风险，这一成果由中山大学徐淼小组经过不懈努力而取得。该研究于2026年4月15日发表于国际一流学术期刊《自然》杂志上。

通过逐步的宿主- EBV基因组相互作用分析，该研究团队发现HLA-A*11:01与EBV高危变体85841G之间的遗传相互作用是NPC风险的关键决定因素。个体携带易感HLA-A背景(HLA-A*11:01（HLA-A*02:07⁺）和感染高危的85841G EBV形成双重风险亚群，其相互作用驱动的NPC风险显著升高，远远超过宿主或病毒单独的影响。这一双重风险亚组占人口的20.5%，约占NPC病例的47%。

研究组发现EBV 85841G编码EBNA3B肽，该肽与HLA-A*11:01结合，引发特异性T细胞反应，能够裂解携带85841G的菌株转化的EBV⁺ B细胞，并且与A*11:01携带者唾液病毒载量降低和鼻咽癌风险降低有关。进化分析表明，85841G是通过北部和南部EBV之间的古老重组事件产生的，随后在中国南方进行了克隆扩增，导致宿主和病毒相互作用的风险因子共同富集，从而促进了NPC的流行。这些发现揭示了NPC中明显分层的、相互作用驱动的风险架构，并强调了精确预防的机会。

据了解，EB病毒（EBV）感染全球95%以上的成年人，但与中国南方的地方性鼻咽癌（NPC）有关。

附：英文原文

Title: EBV strain interacts with host HLA to drive nasopharyngeal carcinoma risk

Author: Chen, Yanhong, Liang, Jingtong, Zhang, Wanlin, Zhang, Xinyu, Zhang, Xinyi, Wang, Ching-Yuan, Yao, Fei, Zhang, Shanshan, Zhou, Xiang, Ye, Weimin, Feng, Ruimei, Cai, Yonglin, Zhang, Zhe, Ji, Mingfang, Cui, Qian, Lin, Xihong, Li, Jiesen, Xu, Jialei, Zhang, Qiuting, Huang, Qinyao, Cheng, Yingying, Luo, Yanran, Ye, Xiaoping, Feng, Qisheng, Tang, Minzhong, Zeng, Mu-Sheng, Zeng, Yi-Xin, Liu, Zhonghua, Zhai, Weiwei, Liu, Jianjun, Xu, Miao

Issue&Volume: 2026-04-15

Abstract: Epstein–Barr virus (EBV) infects more than 95% of adults worldwide but is associated with endemic nasopharyngeal carcinoma (NPC) specifically in southern China1,2,3,4. Here, through a stepwise host–EBV genome interaction analysis, we identify a genetic interaction between HLA-A*11:01 and the high-risk EBV variant 85841G as a key determinant of NPC risk. Individuals carrying a susceptible HLA-A background (HLA-A*11:01 or HLA-A*02:07+) and infected with the high-risk 85841G EBV form a dual-risk subgroup with substantially elevated, interaction-driven NPC risk, far exceeding the effects of host or virus alone. This dual-risk subgroup comprises 20.5% of the population and accounts for approximately 47% of NPC cases. We show that EBV 85841G encodes an EBNA3B peptide that binds to HLA-A*11:01 and elicits specific T cell responses capable of lysing EBV+ B cells transformed by 85841G-carrying strains, and is associated with reduced salivary viral load and lower NPC risk among A*11:01 carriers. Evolutionary analysis reveals that 85841G arose via ancient recombination events between northern and southern EBV and subsequently underwent clonal expansion in southern China, leading to co-enrichment of interacting host and viral risk factors that, in turn, contribute to NPC endemicity. These findings reveal a markedly stratified, interaction-driven risk architecture in NPC and highlight opportunities for precision prevention.

DOI: 10.1038/s41586-026-10416-8

Source: https://www.nature.com/articles/s41586-026-10416-8