Distinct genetic architectures and environmental factors associate with host response to the γ2-herpesvirus infections

Neneh Sallah (), Wendell Miley, Nazzarena Labo, Tommy Carstensen, Segun Fatumo, Deepti Gurdasani, Martin O. Pollard, Alexander T. Dilthey, Alexander J. Mentzer, Vickie Marshall, Elena M. Cornejo Castro, Cristina Pomilla, Elizabeth H. Young, Gershim Asiki, Martin L. Hibberd, Manjinder Sandhu, Paul Kellam, Robert Newton, Denise Whitby and Inês Barroso ()
Additional contact information
Neneh Sallah: The Wellcome Sanger Institute, Wellcome Genome Campus
Wendell Miley: Leidos Biomedical Research Inc.
Nazzarena Labo: Leidos Biomedical Research Inc.
Tommy Carstensen: The Wellcome Sanger Institute, Wellcome Genome Campus
Segun Fatumo: The Wellcome Sanger Institute, Wellcome Genome Campus
Deepti Gurdasani: The Wellcome Sanger Institute, Wellcome Genome Campus
Martin O. Pollard: The Wellcome Sanger Institute, Wellcome Genome Campus
Alexander T. Dilthey: Heinrich Heine University Düsseldorf
Alexander J. Mentzer: University of Oxford
Vickie Marshall: Leidos Biomedical Research Inc.
Elena M. Cornejo Castro: Leidos Biomedical Research Inc.
Cristina Pomilla: The Wellcome Sanger Institute, Wellcome Genome Campus
Elizabeth H. Young: The Wellcome Sanger Institute, Wellcome Genome Campus
Gershim Asiki: African Population and Health Research Center
Martin L. Hibberd: London School of Hygiene & Tropical Medicine
Manjinder Sandhu: University of Cambridge
Paul Kellam: Imperial College London
Robert Newton: MRC/UVRI at the London School of Hygiene & Tropical Medicine
Denise Whitby: Leidos Biomedical Research Inc.
Inês Barroso: The Wellcome Sanger Institute, Wellcome Genome Campus

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: Abstract Kaposi’s sarcoma-associated herpesvirus (KSHV) and Epstein-Barr Virus (EBV) establish life-long infections and are associated with malignancies. Striking geographic variation in incidence and the fact that virus alone is insufficient to cause disease, suggests other co-factors are involved. Here we present epidemiological analysis and genome-wide association study (GWAS) in 4365 individuals from an African population cohort, to assess the influence of host genetic and non-genetic factors on virus antibody responses. EBV/KSHV co-infection (OR = 5.71(1.58–7.12)), HIV positivity (OR = 2.22(1.32–3.73)) and living in a more rural area (OR = 1.38(1.01–1.89)) are strongly associated with immunogenicity. GWAS reveals associations with KSHV antibody response in the HLA-B/C region (p = 6.64 × 10−09). For EBV, associations are identified for VCA (rs71542439, p = 1.15 × 10−12). Human leucocyte antigen (HLA) and trans-ancestry fine-mapping substantiate that distinct variants in HLA-DQA1 (p = 5.24 × 10−44) are driving associations for EBNA-1 in Africa. This study highlights complex interactions between KSHV and EBV, in addition to distinct genetic architectures resulting in important differences in pathogenesis and transmission.

Date: 2020
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DOI: 10.1038/s41467-020-17696-2

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