A study suggests that multiple sclerosis may be triggered by the Epstein-Barr virus, a herpes virus that can cause infectious mononucleosis, also known as the “kissing disease” mono.

The virus is spread most commonly through bodily fluids, especially saliva. However, the virus can also spread through blood and semen during sexual contact, blood transfusions, and organ transplantations.

To explore whether there is a link between multiple sclerosis and the Epstein-Barr virus, a team of researchers studied more than 10 million active-duty US military personnel between 1993 and 2013.

Dr. Alberto Ascherio from the Harvard T.H. Chan School of Public Health led the study and the National Institute of Health’s National Institute of Neurological Disorders and Stroke (NINDS) partly supported the work.

Active-duty soldiers have blood samples taken every two years as part of routine medical screenings. The Department of Defense Serum Repository contains serum left over from these screenings.

From these samples, the researchers determined whether—and when—donors were infected with EBV. They tested samples from 801 people who developed MS. They then compared these to samples from more than 1,500 matched controls (people with similar characteristics who did not develop MS).

The team found a much higher rate of EBV infection among people who developed MS than among controls. Out of the 801 MS cases, only one person tested negative for EBV in their last sample collected before MS onset. The team calculated that people infected with EBV were 32 times as likely to develop MS as uninfected people.

The researchers found no such association between MS and any other human viruses. This included cytomegalovirus, a virus distantly related to EBV that is transmitted similarly.

The team also measured blood levels of neurofilament light chain (NfL), a biomarker for nerve degeneration. NfL levels increased in people who developed MS compared to those who did not. The increase occurred only after EBV infection and usually before MS diagnosis. This finding shows that the nerve degeneration that accompanied MS did not start before infection with EBV.

The researchers say that the association between EBV and MS risk was too strong to be explained by any other known MS risk factors. The findings strongly suggest that EBV is part of the chain of events that leads to most cases of MS. However, EBV in itself is not sufficient to trigger MS, researchers say. Other unknown factors can play a role.

“The hypothesis that EBV causes MS has been investigated by our group and others for several years, but this is the first study providing compelling evidence of causality,” Ascherio says.

“This is a big step because it suggests that most MS cases could be prevented by stopping EBV infection.”