Human genomics of the humoral immune response against polyomaviruses

F Hodel; A Y Chong; P Scepanovic; Z M Xu; O Naret; C W Thorball; S Rüeger; P Marques-Vidal; P Vollenweider; M Begemann; H Ehrenreich; N Brenner; N Bender; T Waterboer; A J Mentzer; A V S Hill; C Hammer; J Fellay

doi:10.1093/ve/veab058

Human genomics of the humoral immune response against polyomaviruses

Virus Evol. 2021 Jun 11;7(2):veab058. doi: 10.1093/ve/veab058. eCollection 2021.

Authors

F Hodel¹, A Y Chong², P Scepanovic³, Z M Xu¹, O Naret¹, C W Thorball¹, S Rüeger⁴, P Marques-Vidal⁵, P Vollenweider⁵, M Begemann⁶, H Ehrenreich⁶, N Brenner⁷, N Bender⁷, T Waterboer⁷, A J Mentzer², A V S Hill², C Hammer⁸, J Fellay¹

Affiliations

¹ Global Health Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.
² The Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, United Kingdom.
³ Roche Pharmaceutical Research and Early Development, F. Hoffmann-La Roche Ltd, Headquarters Grenzacherstrasse 124, CH-4070 Basel, Switzerland.
⁴ Institute for Molecular Medicine Finland, Institute of Life Science HiLIFE, University of Helsinki, Haartmaninkatu 8, 00290 Helsinki, Finland.
⁵ Department of Medicine, Internal Medicine, Lausanne University Hospital and University of Lausanne, Rue du Bugnon 46, CH-1011 Lausanne, Switzerland.
⁶ Clinical Neuroscience, Max Planck Institute of Experimental Medicine, DFG Research Center for Nanoscale Microscopy and Molecular Physiology of the Brain, Hermann-Rein-Straße 3, 37075 Göttingen, Germany.
⁷ Infections and Cancer Epidemiology, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
⁸ The Jenner Institute, University of Oxford, Old Road Campus Research Build, Roosevelt Dr, Oxford OX1 2JD, United Kingdom.

Abstract

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 FUT2, responsible for secretor status, MCPyV with variants in STING1, involved in interferon induction, and WUPyV with a functional variant in MUC1, 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.

Keywords: GWAS; genomics; human; infection; meta-analysis; polyomavirus.