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A study published in Nature looks at genetic determinants of persistent Epstein-Barr virus DNA and associations with chronic conditions.
Prof Lawrence Young, Virologist and Emeritus Professor of Molecular Oncology, University of Warwick, said:
“This study provides new insights into the control of Epstein-Barr virus (EBV) infection and its association with various chronic diseases. EBV is most common virus infection in humans being found as a persistent infection in over 90% of the population worldwide. Using novel computational methods, this study comprehensively analysed a subset of EBV infected individuals who have high levels of detectable EBV in their blood and then correlated this with various diseases and immunological factors. Their findings confirm previously identified associations between EBV and various diseases such as Hodgkin’s lymphoma and systemic lupus erythematous. They also highlight possible associations between high levels of EBV in the blood and chronic obstructive pulmonary disease, chronic ischaemic heart disease, stroke, rheumatoid arthritis, and various neurological conditions. The problem here, as the authors point out, is that correlation does not necessarily mean causation. This is particularly relevant to EBV as this infection is under tight immunological control, as further supported by the genetic association studies in this publication, and anything that affects that general state of the immune system can result in increased levels of EBV in the blood. Nevertheless, this study confirms some previous suspicious associations including the potential relationship between EBV and chronic fatigue syndrome and should stimulate more detailed analysis of the contribution of EBV infection to these chronic conditions. It’s important to note that this methodology failed to produce evidence supporting a role for EBV in multiple sclerosis despite the overwhelming epidemiological and biological evidence confirming this association. This reflects the complex aetiology of chronic diseases and the need for different analytical approaches in determining disease associations. This study highlights the power of large-scale genomic analysis and its ability to provide novel insights into how genetic variation can contribute to the control of a common virus infection and how this contributes to the development of chronic diseases. As regards EBV infection, it provides further impetus to the development of both therapeutic and preventive approaches to targeting EBV infection.“
Prof Chris Ponting, Chair of Medical Bioinformatics and Principal Investigator at the MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, said:
“The authors discovered that about 10% of people have detectable DNA levels of the Epstein-Barr virus (EBV) in their blood. Further, they found that this could predict complex disease, but not sufficiently to be diagnostic or prognostic. Blood EBV level was significantly associated with rheumatoid arthritis, chronic obstructive pulmonary disease (COPD), depression, peripheral vascular disease and hundreds of other diseases and traits. In separate large UK and US samples, people with high EBV levels were twice as likely to have COPD than those with low levels, for example.
“These findings are relevant to over 90% of us who have been infected with this virus. One explanation of their findings is that they “reflect a general state of immunosuppression”, as opposed to blood EBV more directly affecting risk of all of these diseases. The authors predicted that the genetic signature of high EBV blood level is most relevant to B cells and antigen-presenting cells. However, as nearly all of this signature came from only one – the human leukocyte antigen (HLA) region – of the 22 genetic associations, this conclusion may not generalise.
“As a side note, one association they found was between EBV DNA and ‘Malaise and fatigue’ (ICD-10 code R53). After this, they stated “that EBV has long been hypothesized as a risk factor for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)” and “Our results reinforce a potential relationship between EBV and ME/CFS that warrants further examination”. Nevertheless, ME/CFS is not classified under R53 (rather, under G93.3), so this interesting association is not clearly relevant to ME/CFS (which has many other symptoms beyond fatigue), but rather is relevant to asthenia, debility, general physical deterioration, lethargy and tiredness. From their supplementary data, ME/CFS (G93.3) had the opposite effect (i.e., was correlated negatively with EBV DNA levels), albeit not significantly.
“Future work should now focus on identifying and understanding the genes that affect EBV blood levels within their discovered 22 independent loci.”
‘Population-scale sequencing resolves determinants of persistent EBV DNA’ by Sherry S. Nyeo et al. was published in Nature at 16:00 UK time on Wednesday 28th January 2026.
DOI: https://doi.org/10.1038/s41586-025-10020-2
Declared interests
Prof Chris Ponting: “CPP is an Investigator of the DecodeME project (funded by MRC and NIHR) and his group’s research is currently funded by MRC, ME Research UK and philanthropic donations.“
Prof Lawrence Young: “Lawrence Young is consultant to the following companies who are developing novel approaches to the treatment and prevention of EBV-associated diseases – BioNTech, iosBio, flindr therapeutics, AbVir Biotherapeutics.”