Distinct genetic architectures and environmental factors associate with host response to the γ2-herpesvirus infections.
Nat Commun
; 11(1): 3849, 2020 07 31.
Article
in En
| MEDLINE
| ID: mdl-32737300
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sarcoma, Kaposi
/
Epstein-Barr Virus Infections
/
Henipavirus Infections
/
Host-Pathogen Interactions
/
Disease Resistance
/
Antibodies, Viral
Type of study:
Incidence_studies
/
Prognostic_studies
/
Risk_factors_studies
Country/Region as subject:
Africa
Language:
En
Journal:
Nat Commun
Journal subject:
BIOLOGIA
/
CIENCIA
Year:
2020
Document type:
Article
Affiliation country:
Reino Unido