1. Distinct genetic architectures and environmental factors associate with host response to the γ2-herpesvirus infections
- Author
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Denise Whitby, Alexander T. Dilthey, Deepti Gurdasani, Martin L. Hibberd, Wendell Miley, Manjinder S. Sandhu, Cristina Pomilla, Paul Kellam, Nazzarena Labo, Robert U. Newton, Gershim Asiki, Elena M. Cornejo Castro, Vickie Marshall, Alexander J. Mentzer, Elizabeth H. Young, Martin O. Pollard, Inês Barroso, Neneh Sallah, Tommy Carstensen, Segun Fatumo, Sallah, Neneh [0000-0002-2953-5311], Pollard, Martin O [0000-0001-8738-0920], Dilthey, Alexander T [0000-0002-6394-4581], Mentzer, Alexander J [0000-0002-4502-2209], Cornejo Castro, Elena M [0000-0003-1480-1397], Asiki, Gershim [0000-0002-9966-1153], Hibberd, Martin L [0000-0001-8587-1849], Sandhu, Manjinder [0000-0002-2725-142X], Kellam, Paul [0000-0003-3166-4734], Barroso, Inês [0000-0001-5800-4520], Apollo - University of Cambridge Repository, Pollard, Martin O. [0000-0001-8738-0920], Dilthey, Alexander T. [0000-0002-6394-4581], Mentzer, Alexander J. [0000-0002-4502-2209], Cornejo Castro, Elena M. [0000-0003-1480-1397], and Hibberd, Martin L. [0000-0001-8587-1849]
- Subjects
0301 basic medicine ,Male ,Rural Population ,Epstein-Barr Virus Infections ,Herpesvirus 4, Human ,Urban Population ,viruses ,45/43 ,General Physics and Astronomy ,Gene Expression ,Genome-wide association study ,Disease ,Antibodies, Viral ,0302 clinical medicine ,hemic and lymphatic diseases ,Uganda ,lcsh:Science ,Antigens, Viral ,Disease Resistance ,Henipavirus Infections ,Multidisciplinary ,631/208/729 ,Transmission (medicine) ,Coinfection ,Incidence ,virus diseases ,Genomics ,631/208/721 ,631/208/248 ,Middle Aged ,631/208/727 ,030220 oncology & carcinogenesis ,631/208/212 ,Herpesvirus 8, Human ,Host-Pathogen Interactions ,Female ,82/1 ,141 ,Adult ,HIV Positivity ,Genotype ,Adolescent ,Science ,45/23 ,Human leukocyte antigen ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Virus ,Article ,HLA-DQ alpha-Chains ,03 medical and health sciences ,Antigen ,medicine ,Immunogenetics ,Humans ,Sarcoma, Kaposi ,HIV ,General Chemistry ,medicine.disease ,030104 developmental biology ,Epstein-Barr Virus Nuclear Antigens ,Immunology ,Genetic markers ,lcsh:Q ,Heritable quantitative trait ,Capsid Proteins ,Genome-Wide Association Study - 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., Disease prognosis after infection with Kaposi’s sarcoma-associated herpesvirus and Epstein-Barr Virus is highly variable. Here the authors carry out epidemiological and genetic analysis of a Ugandan cohort and suggest complex interactions may influence pathogenesis and transmission.
- Published
- 2020