Compelling Evidence that Epstein Barr Infection is Cause of Multiple Sclerosis

MedicalResearch.com Interview with:
Kassandra L. Munger Sc.D.
Senior Research Scientist
Alberto Ascherio MD Dr.P.H.
Professor of Epidemiology and Nutrition
Harvard T.H. Chan School of Public Health

MedicalResearch.com: What is the background for this study?

Response: An infectious cause of MS has been hypothesized for decades. Research over the past 20 years conducted by our group and others has strongly suggested a role for EBV infection including that EBV-negative individuals have a near zero risk of developing MS, having a history of infectious mononucleosis (caused by EBV infection) increases the risk of MS 2-fold, and healthy individuals have higher risks of MS with higher antibody levels against EBV antigens.  Ideally, to prove causality a randomized clinical controlled trial would be conducted; however, this not a feasible approach in this case. Given that nearly 95% of the adult population is infected with EBV and MS is a rare disease, we utilized the Department of Defense Serum Repository which stores over 60 million serum samples from over 10 million US Military active duty personnel. From this large resource, we were able to identify a cohort who were EBV negative when they joined the military and we followed them for whether they had a primary infection with EBV and then for who developed MS.

MedicalResearch.com: Are there different strains of EBV which may affect the risk of multiple sclerosis?  or different host factors?

Response: There are different strains of EBV, but it is not clear if or how they may differentially affect MS risk.  There does appear to be a synergy between EBV infection and carrying the MS risk allele HLADR*1501, but potential interactions between EBV and other MS risk factors are less clear. 

MedicalResearch.com: What are the main findings? 

Response: We found that becoming infected with EBV increased risk of MS by 32-fold when compared to individuals who were not infected with EBV. Importantly, we also showed that infection with the cytomegalovirus (a virus with a similar transmission route as EBV) did not increase MS risk and the antibody response to ~200 viruses was only statistically significantly different for EBV, which, taken together, indicate that the immune response to EBV in people who develop MS is not due to a generalized immune response, but is EBV-specific.  We also found that primary EBV infection occurs prior to an increase in serum neurofilament light chain, a biomarker for neuronal damage such as that seen in MS, strongly suggesting that EBV infection occurs before the pathological process of MS begins.

MedicalResearch.com: What should readers take away from your report?

Response: Our findings provide compelling evidence that EBV is a cause of MS. The strength of the association cannot be explained by other known risk factors for MS (including genetic susceptibility) and it is extremely unlikely that there a risk factor strong enough to explain the association that has not been discovered yet.

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

Response: With the results of our study, future research has a strong evidence-based causal relationship between EBV and MS on which to build. Increasing research into EBV vaccines for MS prevention and anti-EBV therapies in MS patients should be a major focus of future research.


Kjetil Bjornevik, Marianna Cortese, Brian C. Healy, Jens Kuhle, Michael J. Mina, Yumei Leng, Stephen J. Elledge, David W. Niebuhr, Ann I. Scher, Kassandra L. Munger, Alberto Ascherio. Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis. Science, 2022 DOI: 10.1126/science.abj8222






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Last Updated on January 15, 2022 by Marie Benz MD FAAD