美国麻省理工学院和哈佛大学的布罗德研究所Po-Ru Loh团队的最新研究探明了DNA病毒组随着人类基因和环境的变化而变化。2026年3月25日出版的《自然》发表了这项成果。

本研究利用英国生物银行（n=490401）、"我们所有人"研究项目（n=414817）和西蒙斯基金会自闭症研究计划（SPARK；n=12519）的全基因组测序数据，分析了31种常见病毒在人体血液和唾液中的DNA载量。研究发现，病毒DNA载量随年龄、昼夜节律和季节呈现显著变化；大多数病毒在男性中的载量高于女性。人类基因组中数十个位点的遗传变异与七种病毒的DNA载量相关：EB病毒（45个位点）、人疱疹病毒7型（37个位点）、人疱疹病毒6B型、梅克尔细胞多瘤病毒及三种指环病毒。主要组织相容性复合体位点的变异产生了最显著的相关性（P = 5.8 × 10^-9 至 2.5 × 10^-1459），且每种病毒具有特异性。HLA-B*08:01等位基因还与EB病毒亚型存在宿主-病毒遗传互作（P = 7.4 × 10^-70）。其他人类遗传效应涉及编码抗原肽加工提呈蛋白的基因，如ERAP1（与人疱疹病毒7型相关，P = 2.7 × 10^-78）和ERAP2（与EB病毒相关，P = 4.6 × 10^-111）。孟德尔随机化分析支持EB病毒DNA载量对霍奇金淋巴瘤风险具有强因果效应（P = 1.8 × 10^-3），但与多发性硬化症无显著关联（P = 0.52）。这表明慢性EB病毒高载量增加淋巴瘤风险，而EB病毒感染与自身免疫性疾病的关联则反映了宿主对特定病毒表位的免疫应答。

据介绍，许多病毒已经适应了在被感染的人体内持续生存。宿主对其持续丰度（病毒载量）的可变控制可导致清除或疾病。

附：英文原文

Title: The DNA virome varies with human genes and environments

Author: Kamitaki, Nolan, Tang, David, McCarroll, Steven A., Loh, Po-Ru

Issue&Volume: 2026-03-25

Abstract: Many viruses have adapted to persist in infected humans for life1,2. Variable host control of their ongoing abundance (viral load) can lead to clearance or disease3,4,5. Here we analysed the viral DNA load of 31 common viruses in human blood and saliva using whole-genome sequencing data from UK Biobank (n=490,401), All of Us (n=414,817) and Simons Foundation Powering Autism Research for Knowledge (SPARK; n=12,519). Viral DNA load varied markedly with age, time of day and season; most viruses were also present at greater abundance in men than in women. Human genetic variation at dozens of loci associated with DNA load of seven viruses: Epstein–Barr virus (EBV, 45 loci), human herpesvirus (HHV)-7 (37 loci), HHV-6B, Merkel cell polyomavirus and three anelloviruses. Variation at the major histocompatibility complex (MHC) locus generated the strongest associations (P = 5.8 × 10–9 to 2.5 × 10–1459), which were specific to each virus. The HLA-B*08:01 allele also exhibited a host–virus genetic interaction with EBV subtype (P = 7.4 × 10–70). Other human genetic effects implicated genes encoding proteins that process peptides for antigen presentation, such as ERAP1 (HHV-7, P = 2.7 × 10–78) and ERAP2 (EBV, P = 4.6 × 10–111). Mendelian randomization analyses supported a strong causal effect of EBV DNA load on increased risk of Hodgkin’s lymphoma (P = 1.8 × 10–3), but not multiple sclerosis (P = 0.52). This suggests that higher chronic EBV load increases lymphoma risk, whereas associations of EBV infection with autoimmune conditions reflect host immune responses to particular viral epitopes.

DOI: 10.1038/s41586-026-10288-y

Source: https://www.nature.com/articles/s41586-026-10288-y