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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.

Original publication

DOI

10.1038/s41467-020-17696-2

Type

Journal article

Journal

Nature communications

Publication Date

07/2020

Volume

11

Addresses

The Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK. Neneh.Sallah@lshtm.ac.uk.

Keywords

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