| Title: | Host control of persistent Epstein-Barr virus infection |
| Journal: | Nature |
| Published: | 19 Feb 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41714741/ |
| DOI: | https://doi.org/10.1038/s41586-026-10274-4 |
Publication 17702
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
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. 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. Epistasis with distinct HLA-alleles of MHC class I was observed at the ERAP2 locus. Analysis of individuals with EBV-associated diseases4 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. 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.</p>
18 Authors
- Axel Schmidt
- T. Madhusankha Alawathurage
- Friederike S. David
- Yosuke Ogawa
- Leonard Frach
- Sylvia Richter
- Merle Schaefer
- Carina M. Mathey
- Sabrina K. Henne
- Andreas J. Forstner
- Alexander T. Dilthey
- Anne-Katrin Pröbstel
- Kaan Boztug
- Markus M. Nöthen
- Ho Namkoong
- Yukinori Okada
- Eva C. Beins
- Kerstin U. Ludwig
1 Application
| Application ID | Title |
|---|---|
| 135122 | Elucidating the genetic basis of human traits and diseases across the allelic spectrum |
Enabling scientific discoveries that improve human health