基因和环境对人类病毒组有着深刻的影响.
bioRxiv : the preprint server for biology
|September 18, 2025
概括
人类遗传因素对31种DNA病毒的病毒载量有显著的影响,特别是爱斯坦-巴尔病毒 (EBV). 较高的EBV负载因果上会增加霍奇金淋巴瘤风险,但不会增加多发性硬化症风险.
科学领域:
- 人类病毒学 人类病毒学
- 遗传学 是一个遗传学.
- 免疫学 免疫学 免疫学
背景情况:
- 许多病毒在人体中长期存在,病毒载量变化会影响疾病.
- 宿主遗传因素在控制病毒的数量方面发挥着至关重要的作用.
研究的目的:
- 在一个大型的人类队列中分析31个DNA病毒的病毒载荷变异.
- 为了确定与病毒载荷相关的人类遗传位置.
- 调查爱斯坦-巴尔病毒 (EBV) 负载和特定疾病之间的因果关系.
主要方法:
- 来自英国生物银行,SPARK和我们所有人队伍 (n > 600,000) 的全基因组测序数据.
- 对血液和唾液中的31种DNA病毒的病毒载荷分析.
- 全基因组关联研究 (GWAS) 以确定与病毒载荷相关的遗传位置.
- 门德尔随机化评估EBV负载对多发性硬化症和霍奇金淋巴瘤的因果关系.
主要成果:
- 病毒载量因年龄,白天的时间,季节和性别而有显著变化.
- 数十个人类遗传位置与7种病毒的负载有关,特别是EBV (45个位置) 和人类疹病毒7 (HHV-7,24个位置).
- 人类白细胞抗原 (HLA) 复合体显示出与病毒载荷最强的关联,特定的HLA基因基因表现出病毒和特定部位的影响.
- 参与抗原呈现的基因,如ERAP1和ERAP2,也与此有关.
- 高的EBV病毒载量与增加的霍奇金淋巴瘤风险 (OR=19.81) 有因果关系,但不与多发性硬化症风险 (p=0.52) 有因果关系.
结论:
- 人类遗传变异,特别是HLA复合体和抗原处理基因中的变异,深刻影响病毒载量.
- 慢性高EBV病毒载量是霍奇金淋巴瘤的重要危险因素.
- EBV与自身免疫性疾病的关联可能反映了对特定病毒表位的免疫反应,而不是病毒载荷本身.
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