Research Suggests Epstein-Barr Virus Raises Risk of Multiple Sclerosis

Still, experts stressed that other environmental and genetic factors also matter.

Like many autoimmune diseases, multiple sclerosis (MS) causes chronic inflammation. It's the work of the body's immune system, attacking what it's meant to protect. And in the case of MS, the body attacks its myelin sheath, a protective covering for the nerves in the brain and spinal cord.

Researchers have previously struggled to figure out what triggers a body with MS to turn on itself. But some have found some of the most compelling evidence that it could be a common infection, precisely one caused by the Epstein-Barr virus (EBV).

The findings come from a study published in January 2022 in the journal Science. Though the researchers recognized that EBV is not the only risk factor for MS, they suggested that EBV is the leading cause of the condition. 

Here, experts in the field of MS helped parse out the study and explained what the findings mean for your health.

Multiple Sclerosis (MS) Definition

Multiple sclerosis (MS): A nervous system disease that disrupts communication between the brain and other body parts. It is considered an autoimmune disease because MS causes damage to the myelin sheath that protects the nerves.

EBV and MS connection
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What Causes Multiple Sclerosis?

Though researchers have previously suspected that EBV is one of the top risk factors for developing MS, there are several potential causes of the illness.

"A mixture of environmental triggers in a genetically susceptible host is what likely leads to the disease," Claire S. Riley, MD, assistant professor of neurology at Columbia University Medical Center and clinical director of the Multiple Sclerosis Center, told Health

In addition to EBV, research has found several other risk factors of MS, some of which include:

  • Smoking
  • Low sun exposure
  • Pregnancy
  • Childhood obesity

Genetics also play a vital role in the development of MS. Dr. Riley added that researchers have found about 100 genes that may contribute to a person's risk.

However, concerning EBV, causality has been hard to study. For example, you can't purposefully infect people with EBV to see who develops MS. Therefore, a randomized controlled trial is out of the question. 

The group of scientists who conducted the 2022 study, led by Harvard T.H. Chan School of Public Health researchers, got around this issue by conducting an "experiment of nature." Essentially, they watched scenarios play out naturally in an investigation over time.

What Happened During the Study?

In collaboration with the U.S. Armed Forces, the research team examined data—collected from serum samples—from more than 10 million people on active duty. The researchers collected the data between 1993 and 2013. 

The samples, left over from HIV blood tests performed biennially on active-duty service members, were used to identify EBV status and the relation between EBV infection and MS onset.

Of the 10 million active-duty members, researchers identified 955 cases of MS. But only 801 had serum samples available to assess EBV status. All but one of the MS cases tested positive for EBV antibodies at the time of MS onset, meaning they had previously had the infection.

What Does the Study Say About EBV's Link to MS?

Overall, the risk of MS increased 32-fold after an EBV infection but remained unchanged after contracting other viruses like cytomegalovirus (CMV). Researchers also found a median five-year gap between the first EBV-positive serum sample and the onset of MS.

The authors stated that any other known risk factor could not explain those findings and suggested that EBV is the leading cause of MS. 

"The hypothesis that EBV causes MS has been investigated by our group and others for several years," Alberto Ascherio, MD, DrPH, professor of epidemiology and nutrition at Harvard T.H. Chan School of Public Health and senior author of the study, said in a press release. "But this is the first study providing compelling evidence of causality."

Does This Mean if You've Had EBV, You'll Get MS?

No, it just means that if you've had EBV, you may have a higher risk of developing MS than someone who hasn't. You may or may not be aware of whether you've had EBV. Sometimes, it can cause infectious mononucleosis, while other times, EBV can feel like a brief cold- or flu-like illness.

In a perspective piece also published in ScienceWilliam H. Robinson, MD, PhD and Lawrence Steinman, MD, professors from the Department of Medicine at Stanford University, explained that nearly everyone is infected with EBV at some point. But only a small fraction of those people develop MS. That means other risk factors must be present for the development of MS.

Still, Dr. Riley said the results of the 2022 study provide the most convincing evidence researchers have seen that EBV could trigger MS. And in the future, that information could go on to prevent both EBV and potentially MS.

What’s the Benefit of This Study for the General Public?

As of November 2022, there's no vaccine available to help prevent EBV. But the 2022 study adds to evidence that one may be increasingly necessary.

"The conversation is shifting from 'how can we reduce risk of MS in the population?' to 'how can we prevent MS from occurring in the first place?'" Kassandra L. Munger, ScD, MS, project director at the Harvard T. H. Chan School of Public Health and one of the study authors, told Health. "I think this opens up avenues in other areas because EBV can contribute to other diseases, as well. [And] an EBV vaccine may not only prevent MS but also other conditions, so I think there's a lot of promise."

To that end, in January 2022, Moderna announced that an EBV vaccine was in the works. At that time, Moderna had begun clinical trials for their mRNA EBV vaccine. Moderna previously used the same type of technology to create its COVID-19 vaccine.

By January 2022, one person had been dosed with the vaccine. But Moderna had planned to enroll approximately 270 participants between 18 and 30, hoping that the vaccine would prevent EBV-induced infectious mononucleosis and potentially EBV infection.

An EBV vaccine could serve as a primary preventative strategy. Understanding the relationship between EBV and MS may also help with public awareness of why people might be offered another vaccine in the future.

Does This Study Help People Who Currently Have MS?

While an EBV vaccine may help prevent MS in the future, it may not help people who already live with the disease. 

But those results may also shape future MS therapies, Martin I. Belkin, DO, a neurologist and medical director of the Michigan Institute for Neurological Disorders' Multiple Sclerosis Center (not involved in the study), told Health. In other words, researchers can focus on treatments that target EBV infection or immune cells infected with EBV.

"I think there's a reason for great hope for the future of patients with MS and reducing the incidence of MS overall in our population," said Dr. Belkin.

A Quick Review

It's unclear what causes MS. But researchers have previously hypothesized that environmental and genetic factors play a role in the development of MS. 

The 2022 study has shown that there may be a link between EBV and MS. In addition to the 2022 study, other research has influenced the early development of a vaccine to mitigate the spread of EBV, which may prevent people from acquiring MS.

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  2. National Library of Medicine. Multiple sclerosis.

  3. Waubant E, Lucas R, Mowry E, et al. Environmental and genetic risk factors for MS: an integrated reviewAnn Clin Transl Neurol. 2019;6(9):1905-1922. doi:10.1002/acn3.50862

  4. Ferrè L, Filippi M, Esposito F. Involvement of genetic factors in multiple sclerosis. Front Cell Neurosci. 2020;14:612953. doi:10.3389/fncel.2020.612953

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  6. National Library of Medicine. Mononucleosis (mono) tests.

  7. Robinson WH, Steinman L. Epstein-Barr virus and multiple sclerosis. Science. 2022;375(6578):264-265. doi:10.1126/science.abm7930

  8. Moderna. Moderna announces first participant dosed in phase 1 study of its mRNA Epstein-Barr virus (EBV) vaccine.

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