Hodel F, Chong A Y, Scepanovic P, Xu Z M, Naret O, Thorball C W, Rüeger S, Marques-Vidal P, Vollenweider P, Begemann M, Ehrenreich H, Brenner N, Bender N, Waterboer T, Mentzer A J, Hill A V S, Hammer C, Fellay J
Global Health Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.
The Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, United Kingdom.
Virus Evol. 2021 Jun 11;7(2):veab058. doi: 10.1093/ve/veab058. eCollection 2021.
Human polyomaviruses are widespread in humans and can cause severe disease in immunocompromised individuals. To identify human genetic determinants of the humoral immune response against polyomaviruses, we performed genome-wide association studies and meta-analyses of qualitative and quantitative immunoglobulin G responses against BK polyomavirus (BKPyV), JC polyomavirus (JCPyV), Merkel cellpolyomavirus (MCPyV), WU polyomavirus (WUPyV), and human polyomavirus 6 (HPyV6) in 15,660 individuals of European ancestry from three independent studies. We observed significant associations for all tested viruses: JCPyV, HPyV6, and MCPyV associated with human leukocyte antigen class II variation, BKPyV and JCPyV with variants in , responsible for secretor status, MCPyV with variants in , involved in interferon induction, and WUPyV with a functional variant in , previously associated with risk for gastric cancer. These results provide insights into the genetic control of a family of very prevalent human viruses, highlighting genes and pathways that play a modulating role in human humoral immunity.
人多瘤病毒在人群中广泛存在，可在免疫功能低下个体中引发严重疾病。为了确定针对多瘤病毒的体液免疫反应的人类遗传决定因素，我们对来自三项独立研究的15660名欧洲血统个体针对BK多瘤病毒（BKPyV）、JC多瘤病毒（JCPyV）、默克尔细胞多瘤病毒（MCPyV）、WU多瘤病毒（WUPyV）和人类多瘤病毒6型（HPyV6）的定性和定量免疫球蛋白G反应进行了全基因组关联研究和荟萃分析。我们观察到所有测试病毒均存在显著关联：JCPyV、HPyV6和MCPyV与人类白细胞抗原II类变异相关，BKPyV和JCPyV与负责分泌状态的基因变异相关，MCPyV与参与干扰素诱导的基因变异相关，WUPyV与一个功能性变异相关，该变异先前与胃癌风险相关。这些结果为一类非常普遍的人类病毒的遗传控制提供了见解，突出了在人类体液免疫中起调节作用的基因和途径。
