美国纪念斯隆-凯特琳癌症中心Caleb A. Lareau小组取得一项新突破。他们的研究显示，群体规模测序解决持久性EBV DNA的决定因素。相关论文于2026年1月28日发表在《自然》杂志上。

在这里，该课题组研究人员证明了现有的人类种群全基因组测序（WGS）数据可以被主题化，以量化持久性EBV DNA。使用WGS和来自UK Biobank的健康记录数据(n=490560)和课题组研究人员所有人(n=245394)，课题组研究人员发现血液来源的EBV DNA定量与呼吸、自身免疫、神经和心血管疾病之间存在可重复的关联。该课题组通过基因组关联研究评估了持久性EBV DNA的遗传决定因素，揭示了148个基因中免疫相关调控区域的遗传富集和蛋白质改变变体。这些基因座的单细胞和通路水平分析表明，可变抗原加工是EB病毒DNA持久性的主要决定因素。

此外，相关基因程序在B细胞和抗原提呈细胞中富集，与它们在病毒库和清除中的作用一致。人类白细胞抗原基因分型和预测病毒表位呈递亲和力暗示主要组织相容性复合体II类变异是EBV持久性的关键调节剂。总之，他们的分析表明，重新分析人类种群规模的WGS数据可以阐明病毒DNA持久性的遗传结构，这是一个可以推广到更广泛的人类病毒组的框架。

据了解，EBV病毒是一种地方性疱疹病毒，与自身免疫、癌症和神经系统疾病有关。虽然原发性感染通常是亚临床的，但持续的EBV感染可导致免疫失调和长期并发症。尽管感染无处不在，初次暴露后EBV持续存在的决定因素仍然知之甚少，尽管人类遗传变异部分有助于这种表型谱。

附：英文原文

Title: Population-scale sequencing resolves determinants of persistent EBV DNA

Author: Nyeo, Sherry S., Cumming, Erin M., Burren, Oliver S., Pagadala, Meghana S., Gutierrez, Jacob C., Ali, Thahmina A., Kida, Laura C., Chen, Yifan, Chu, Hoyin, Hu, Fengyuan, Zou, Xueqing Zoe, Hollis, Benjamin, Fabre, Margarete A., MacArthur, Stewart, Wang, Quanli, Ludwig, Leif S., Dey, Kushal K., Petrovski, Slav, Dhindsa, Ryan S., Lareau, Caleb A.

Issue&Volume: 2026-01-28

Abstract: Epstein–Barr virus (EBV) is an endemic herpesvirus implicated in autoimmunity, cancer and neurological disorders. Although primary infection is often subclinical, persistent EBV infection can drive immune dysregulation and long-term complications. Despite the ubiquity of infection, the determinants of EBV persistence following primary exposure remain poorly understood, although human genetic variation partially contributes to this phenotypic spectrum1,2,3. Here we demonstrate that existing whole genome sequencing (WGS) data of human populations can be used to quantify persistent EBV DNA. Using WGS and health record data from the UK Biobank (n=490,560) and All of Us (n=245,394), we uncover reproducible associations between blood-derived EBV DNA quantifications and respiratory, autoimmune, neurological and cardiovascular diseases. We evaluate genetic determinants of persistent EBV DNA via genome association studies, revealing heritability enrichment in immune-associated regulatory regions and protein-altering variants in 148 genes. Single-cell and pathway level analyses of these loci implicate variable antigen processing as a primary determinant of EBV DNA persistence. Further, relevant gene programs were enriched in B cells and antigen-presenting cells, consistent with their roles in viral reservoir and clearance. Human leukocyte antigen genotyping and predicted viral epitope presentation affinities implicate major histocompatibility complex class II variation as a key modulator of EBV persistence. Together, our analyses demonstrate how re-analysis of human population-scale WGS data can elucidate the genetic architecture of viral DNA persistence, a framework generalizable to the broader human virome4.

DOI: 10.1038/s41586-025-10020-2

Source: https://www.nature.com/articles/s41586-025-10020-2