• Abstract Epstein-Barr virus (EBV) infects ≈90-95% of the global population1,2 and persists in B cells as a life-long infection3. • Prior EBV-infection is associated with autoimmune and neoplastic disease4. • Still, the biological basis of host control during EBV persistence remains unclear. • Here, we report the identification of non-genetic and genetic factors that are associated with EBV control during persistent infection. • Using blood-based genome sequence (GS) data from 486,315 UK Biobank and 336,123 All of Us participants, we identified short read-pairs mapping to the EBV genome in 16.2% and 21.8% of individuals, respectively. • EBV-read detection (EBVread+) reflects increased viral load in blood cells, as shown by orthogonal measurements, and was associated with HIV infection, immunosuppressive drug intake, and current smoking.
Article Summaries:
- A large‑scale analysis of whole‑genome sequencing data from 822,438 participants identified Epstein-Barr virus (EBV) DNA in 16-22 % of individuals, indicating higher viral loads in blood. EBV‑positive status correlated with HIV infection, immunosuppressive drug use, and smoking. Genome‑wide association studies uncovered strong links to the MHC region, including 54 independent HLA‑alleles, and 27 non‑MHC loci, with epistatic interaction at ERAP2. Individuals with multiple sclerosis and rheumatoid arthritis carried a higher polygenic burden of EBV‑associated HLA alleles. Phenome‑wide scans revealed shared genetic risk with inflammatory bowel disease, hypothyroidism, and type 1 diabetes. The study demonstrates that routine genome sequencing can serve as a surrogate marker for EBV load, facilitating research and potential therapies for persistent viral infections.
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