EBV is Likely the Leading Cause of Multiple Sclerosis (MS)

A major study published in Science followed more than 10 million U.S. military personnel and found compelling evidence that infection with the Epstein-Barr virus (EBV) is the trigger for most cases of multiple sclerosis (MS).

Of the 801 individuals who developed MS during the study, all but one had tested positive for EBV before their MS symptoms began. This makes EBV the strongest known risk factor for MS, raising the chances of developing the disease by 32 times after infection.

📌 “Only one of the 801 MS cases occurred in an individual who was EBV-negative in the last sample… The HR for MS comparing EBV seroconversion versus persistent EBV seronegativity was 32.4.”
— Bjornevik et al., Science, 2022

HR stands for hazard ratio, a statistical measure used to show how much the risk of something (like developing MS) increases or decreases over time between two groups.

Seroconversion means the moment your body first starts producing detectable antibodies to a virus, in this case, EBV. It’s how scientists know when someone first became infected and transitioned from seronegative to seropositive.

Seronegativity means that a person does not have detectable antibodies to a particular virus in their blood, indicating they have not yet been infected.

Researchers examined blood samples collected over several years and discovered that nerve damage—a hallmark of MS—only appeared after EBV infection, not before. Other viruses, like cytomegalovirus, did not show the same link.

📌 “sNfL levels… increased after EBV infection. Thus, there were no signs of neuroaxonal degeneration before EBV seroconversion.”
— Bjornevik et al., Science, 2022

sNfL stands for serum neurofilament light chain, a biomarker of nerve damage. Higher levels in the blood suggest that neurons (nerve cells) are breaking down—something that happens in MS.

They also ruled out other possible explanations, such as general immune problems or random chance, but only EBV stood out.

📌 “The overall antibody response to viral peptides was similar in cases and controls at both time points, except for EBV… arguing against a second hit from another virus playing a major role.”
— Bjornevik et al., Science, 2022

The researchers used a tool called VirScan to scan each person’s blood for antibodies to hundreds of viruses, not just EBV. They did this both before and after the person’s MS symptoms began. They found no big differences in antibody responses to other viruses between people who developed MS and those who didn’t. Except for EBV, which had a much stronger antibody response in the people who developed MS. This suggests that people with MS weren’t more vulnerable to viruses in general, just to EBV specifically.

This research suggests that EBV may be the leading cause of MS, and that a vaccine or treatment targeting this virus could one day help prevent the disease entirely.

Citation

Kjetil Bjornevik et al., Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis. Science 375,296-301(2022). DOI:10.1126/science.abj8222