Host control of persistent Epstein-Barr virus infection.
Schmidt A, Alawathurage TM, David FS, Ogawa Y, Frach L, Richter S, Schaefer M, Mathey CM, Henne SK; Japan COVID-19 Task Force; Forstner AJ, Dilthey AT, Pröbstel AK, Boztug K, Nöthen MM, Namkoong H, Okada Y, Beins EC, Ludwig KU. Nature. 2026. doi: 10.1038/s41586-026-10274-4. Online ahead of print.
Epstein-Barr virus (EBV) infects ≈90-95% of the global population and persists in B cells as a life-long infection. Prior EBV-infection is associated with autoimmune and neoplastic (cancer) disease. 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 EBVcontrol 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. Genome-wide analyses of EBVread+ identified strong associations at the Major Histocompatibility Complex (MHC), including 54 independent HLA-alleles of MHC class I and II, and at 27 genomic regions outside MHC.…Analysis of individuals with EBV-associated diseases revealed a higher polygenic burden of EBVread+ for HLA-alleles at MHC class I in multiple sclerosis (driven by HLA-A*02:01), and at MHC class II in rheumatoid arthritis. (HLA-A*0201 is associated with MS resistance and lack of EBV viral load in other studies, Why no associated with HLA-DR B1:1501?). Phenome-wide analyses identified a polygenic overlap of EBVread+ with inflammatory bowel disease, hypothyroidism, and type 1 diabetes. Our study establishes by-products of human GS as a surrogate marker of EBV viral load. This will facilitate investigation and treatment for EBV and other persistent viral infections.
Source: multiple-sclerosis-research.org