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

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Miley, Wendell 
Labo, Nazzarena 
Carstensen, Tommy 
Fatumo, Segun 


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.



Adolescent, Adult, Antibodies, Viral, Antigens, Viral, Capsid Proteins, Coinfection, Disease Resistance, Epstein-Barr Virus Infections, Epstein-Barr Virus Nuclear Antigens, Female, Gene Expression, Genome-Wide Association Study, HIV, HLA-DQ alpha-Chains, Henipavirus Infections, Herpesvirus 4, Human, Herpesvirus 8, Human, Host-Pathogen Interactions, Humans, Incidence, Male, Middle Aged, Rural Population, Sarcoma, Kaposi, Uganda, Urban Population

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Nat Commun

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Springer Science and Business Media LLC