A large-scale study reveals that about one in ten people carry genetic variants making them more vulnerable to severe effects from the Epstein-Barr virus, which infects over 90 percent of the population. These variants are linked to higher viral persistence and increased risks of autoimmune diseases like multiple sclerosis and lupus. The findings, based on over 735,000 genomes, suggest pathways for targeted treatments and vaccines.
The Epstein-Barr virus (EBV), first identified in 1964 in connection with Burkitt’s lymphoma, infects more than 90 percent of people worldwide, often causing infectious mononucleosis that resolves in weeks. However, it has been increasingly tied to long-term autoimmune conditions. A 2022 study provided strong evidence linking EBV to multiple sclerosis, where nerve sheaths are damaged, impairing mobility. Similar connections exist with lupus and rheumatoid arthritis.
Researchers, led by Caleb Lareau at Memorial Sloan Kettering Cancer Center in New York, analyzed genomes from 735,000 participants in the UK Biobank and the US All of Us cohort. Using blood samples, they detected EBV DNA persistence: 9.7 percent of participants (47,452 individuals) retained more than 1.2 complete EBV genomes per 10,000 cells, indicating incomplete viral clearance.
The team identified 22 genomic regions associated with elevated EBV levels, many previously linked to immune diseases. The strongest ties involved variants in major histocompatibility complex (MHC) genes, which help distinguish self from pathogens. These variants impair EBV detection, allowing persistent infection that may trigger immune attacks on the body.
"This virus does something to our immune system, and it does something persistent and permanent to our immune system in some people," says Ruth Dobson at Queen Mary University of London. The variants also correlated with higher risks of autoimmune disorders and fatigue, potentially relating to chronic fatigue syndrome, though the exact link remains unclear.
Chris Wincup at King’s College London, not involved in the study, notes: "Almost everyone is exposed to EBV... How come everyone is exposed to the same virus and that virus causes autoimmunity, yet the majority of people don’t end up with an autoimmune condition?" The results highlight immune components for targeted therapies and underscore the need for EBV vaccines, despite the virus often seeming benign.
Published in Nature, the study offers hope for mitigating EBV's severe impacts on a subset of the population.
