Epstein-Barr Virus Implicated as Cause of Multiple Sclerosis

Harvard researchers uncover powerful association between EBV and MS, raising hopes for prevention or a cure. 

Conceptual illustration of neural networks in the human brain.

Conceptual illustration of neural networks in the human brain.Art by Niko Yaitanes/Harvard Magazine; images by Unsplash  

A team of researchers at the Harvard T. H. Chan School of Public Health (HSPH) say they have discovered circumstantial evidence showing that multiple sclerosis is caused by infection with the Epstein-Barr virus. The research was published online today in the journal Science.  

Multiple sclerosis (MS) is a disease in which the immune system attacks the protective sheaths that cover nerve fibers, leading to muscle weakness, numbness, pain, fatigue, loss of coordination and balance, and other symptoms. The disease, which is incurable, affects 2.8 million people worldwide. But if the HSPH findings prove correct, it might be possible to prevent MS, either by developing a vaccine against the Epstein-Barr virus (EBV) or by developing antiviral drugs to treat EBV infection.  

Alberto Ascherio, professor of epidemiology and nutrition and senior author of the study, has been investigating the hypothesis that Epstein-Barr virus causes multiple sclerosis for several years. But establishing a causal relationship between the two ailments has been difficult because EBV infects most adults (many with no obvious sign of illness), MS is relatively rare, and the symptoms of MS typically begin a decade after EBV infection.

Animation showing dissemination of MS patient brain lesions as illustrated by monthly MRI images taken during the course of a year. 
Image in the public domain

To detect the connection between the two diseases, the researchers analyzed blood samples taken every other year from 10 million current and former active-duty U.S. servicemen and -women, and identified 955 who were diagnosed with MS during their military service. By analyzing samples of these patients’ blood before they became ill, the scientists were able to determine that the risk of developing MS increased 32 times after infection with EBV, but not after infection with any other viruses.

While the study doesn’t prove causality, or describe a mechanism by which EBV leads to MS [UPDATED JANUARY 26, 2022 to describe a causal mechanism uncovered by researchers at Stanford—see below], it is large enough and the association strong enough that it may spark EBV vaccine development. It is even possible, says Ascherio, that “EBV-specific antiviral drugs could ultimately prevent or cure MS.” Other Harvard researchers who contributed to the study include former assistant professor of epidemiology Michael Mina, research scientists Kjetil Bjornevik, Marianna Cortese, and Kassandra Munger,  Mendel professor of genetics and of medicine Stephen Elledge, and associate professor of neurology Brian C. Healy. 


Updated January 26, 2022: A team of Stanford researchers has described a mechanism by which Epstein-Barr Virus induces an autoimmune attack on the myelin sheaths that protect nerves. The scientists detected an antibody in the cerebrospinal fluid of MS patients that attacks both EBV and a central nervous system protein that is structurally similar at a molecular level. The work was published January 24, 2022 in Nature. An investigational therapy developed by Atara biotherapeutics, working with some of the Stanford authors, is currently in clinical study; an mRNA vaccine against EBV, developed by Moderna, is currently in clinical trials.

Read more articles by: Jonathan Shaw

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