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Distinct genetic architectures and environmental factors associate with host response to the gamma 2-herpesvirus infections

  1. Author:
    Sallah, Neneh [ORCID]
    Miley, Wendell
    Labo, Nazzarena
    Carstensen, Tommy
    Fatumo, Segun
    Gurdasani, Deepti
    Pollard, Martin O [ORCID]
    Dilthey, Alexander T [ORCID]
    Mentzer, Alexander J [ORCID]
    Marshall, Vickie
    Cornejo Castro, Elena M [ORCID]
    Pomilla, Cristina
    Young, Elizabeth H
    Asiki, Gershim [ORCID]
    Hibberd, Martin L [ORCID]
    Sandhu, Manjinder [ORCID]
    Kellam, Paul [ORCID]
    Newton, Robert
    Whitby, Denise
    Barroso, Inês [ORCID]

  2. Author Address

    The Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK. Neneh.Sallah@lshtm.ac.uk., London School of Hygiene & Tropical Medicine, London, UK. Neneh.Sallah@lshtm.ac.uk., Viral Oncology Section, AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc., Frederick, MD, USA., Department of Medicine, University of Cambridge, Cambridge, UK., MRC/UVRI at the London School of Hygiene & Tropical Medicine, Entebbe, Uganda., Queen Mary University London, London, UK., Institute of Medical Microbiology and Hospital Hygiene, Heinrich Heine University D 252;sseldorf, 40225, D 252;sseldorf, Germany., Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK., Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK., African Population and Health Research Center, Nairobi, Kenya., Department of Infectious Diseases, Imperial College London, London, UK., Kymab Ltd, Babraham Research Complex, Cambridge, UK., The Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK. ines.barroso@exeter.ac.uk., MRC Epidemiology Unit, University of Cambridge, Cambridge, UK. ines.barroso@exeter.ac.uk., Exeter Centre of ExcEllence in Diabetes (ExCEED), University of Exeter Medical School, Exeter, UK. ines.barroso@exeter.ac.uk.,
    1. Year: 2020
    2. Date: Jul 31
    3. Epub Date: 2020 07 31
  2. Journal: Nature communications
    1. 11
    2. 1
    3. Pages: 3849
  4. Type of Article: Article
  5. Article Number: 3849
  6. ISSN: 2041-1723
  1. 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.

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External Sources

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  2. DOI: 10.1038/s41467-020-17696-2
  3. PMID: 32737300
  4. View record in Web of Science®
  5. WOS: 000560399300011
  6. PII : 10.1038/s41467-020-17696-2

Library Notes

  1. Fiscal Year: FY2019-2020
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