The traditional thinking that multiple sclerosis (MS) is an autoimmune disease of unknown aetiology is being challenged by new findings showing that it is strongly associated with Epstein-Barr virus (EBV) infection.

A study of blood samples from young military recruits conducted by Harvard T.H. Chan School of Public Health researchers showed that the risk of MS in later life increased 32-fold among those who developed infection with EBV compared to uninfected people, and was unchanged after infection with other viruses.

In a retrospective study of blood samples taken from 10 million newly-enlisted military personnel under the age of 20 used for HIV testing researchers noted that only 5% did not initially have EBV infection.

The team identified 801 people who developed MS, typically after ten years, and compared them to 1,566 controls without MS whose samples were available.

The results, published online in the journal Science showed that  in the first blood samples taken, only 35 of the people who developed MS and 107 of controls were negative for EBV infection.  Tracking samples of 801 people with MS over time, the team found that only one had not been infected with Epstein-Barr before the onset of MS, equivalent to a 32-fold increased risk compared to uninfected people.

There was also no such increase in risk of developing MS seen with other viruses such as cytomegalovirus. The researchers led by  Professor Alberto Ascherio, also noted that in people with MS who were EBV negative at the beginning of the study, there was no indication of elevated neurofilament light chain (NfL) until they were infected with EBV. After infection, elevated levels were detected prior to the MS diagnosis.

Professor Ascherio said the delay between EBV infection and the onset of MS may be partially due to the disease’s symptoms being undetected during the earliest stages and partially due to the evolving relationship between EBV and the host’s immune system, which is repeatedly stimulated whenever latent virus reactivates.

“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,” he said.

“This is a big step because it suggests that most MS cases could be prevented by stopping EBV infection, and that targeting EBV could lead to the discovery of a cure for MS.”

“Currently there is no way to effectively prevent or treat EBV infection, but an EBV vaccine or targeting the virus with EBV-specific antiviral drugs could ultimately prevent or cure MS.,” he suggested.

An accompanying commentary published in Science by immunologists Professor William Robinson and Professor Lawrence Steinman at Stanford University, California, concluded that: “These findings provide compelling data that implicate Epstein-Barr virus as the trigger for the development of multiple sclerosis.”

“Now that the initial trigger for multiple sclerosis has been identified, perhaps multiple sclerosis could be eradicated,” they wrote.

The National MS Society, which part sponsored the study ,was cautious about drawing conclusions about whether the Epstein-Barr virus causes relapses or influences the MS disease course.

The Society also noted that EBV infection is widespread and there is currently no way to avoid infection by the Epstein-Barr virus, although antivirals and anti-EBV vaccines are in development.

“The Epstein-Barr virus is easily passed between people and most people have already been exposed. There are vaccines in development that, if proven safe and effective, should be tested in people who are at higher risk for MS, such as people with close family members with MS,” it said.

“It is possible in the future an EBV vaccine could prevent MS. We know that this virus does not act alone, but rather in combination with other risk factors such as a person’s genes and environment. In addition to the possibility of an EBV vaccine, researchers are working on ways to calibrate any individual’s personal risk for developing MS to provide a possible rationale for intervening before it takes hold.”