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

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Author(s)

  • 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
  • Inês Barroso

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Publication details

JournalNature Communications
DateAccepted/In press - 13 Jul 2020
DatePublished (current) - 31 Jul 2020
Issue number1
Volume11
Original languageEnglish

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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© 2020, The Author(s).

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