Harvard Researchers Identify Epstein-Barr Virus as a Cause of MS

A longitudinal study of 10 million people in the U.S. military shows the link. The researchers say genetic predisposition, other factors are likely needed for the viral infection to cause multiple sclerosis.

Epstein-Barr virus may be the main cause of multiple sclerosis (MS), a progressive and incurable neurological disease afflicting 2.8 million people worldwide, a new study reveals.

Results of the study — led by researchers at the Harvard T.H. Chan School of Public Health — were published online in Science on Jan. 13.

To explore the potential link between EBV and MS, the Harvard researchers evaluated more than 10 million young adults on active duty in the U.S. military, measuring EBV antibodies in blood serum samples stored by the Department of Defense. They identified 955 service members diagnosed with MS. Those infected with EBV after joining the military had a heightened risk of developing MS compared to those who did not contract the virus.

As a chronic inflammatory disease of the central nervous system, MS wreaks havoc on the myelin sheaths, insulating layers of fatty tissue that safeguard neurons in the brain and spinal cord. EBV is a herpes virus that triggers infectious mononucleosis and continues to lurk inside the body for life. The exact mechanism by which it could cause MS remains unclear.

Substantiating EBV’s causal role in MS has been fraught with challenges, partly because EBV infections are so common. About 95% of adults get infected with the virus, yet only a tiny fraction of people ever develops MS. Moreover, the onset of MS symptoms occurs, on average, a decade after EBV infection, and some studies have found that MS develops 30 years after the EBV caused mononucleosis, says Kassandra Munger, Sc.D., a senior research scientist at Harvard public health school and one of the study’s two senior co-authors.

“We can consider EBV necessary to developing MS, but there need to be other mitigating factors, such as a genetic predisposition,” says Munger. Cigarette smoking, vitamin D deficiency and obesity, particularly early in life, could play a role in whether EBV infection leads to MS.

The researchers suspect that that the time lag between EBV infection and MS onset could stem, in part, from the MS symptoms not occurring during the initial pathophysiology. Another factor may be that the relationship between viral infection and the immune system may evolve, with the latent infection reactivating due to persistent stimulation.

There are antiviral medications that can help control infection, but no drugs for MS that specifically target EBV. The researchers expressed hope for development of an EBV vaccine or EBV-specific antiviral drugs — and an EBV vaccine may be in the works. In early January, Moderna launched early-stage clinical trials in humans to test an mRNA vaccine against the EBV virus. The company expects to assess the vaccine’s safety and dosage in about 270 participants.

“Moderna is committed to developing a portfolio of first-in-class vaccines against latent viruses for which there are no approved vaccines today,” Stéphane Bancel, the company’s chief executive officer, said in a prepared statement.

If the trial shows that the experimental vaccine is safe and has some efficacy, the same mRNA technology underpinning Moderna’s COVID-19 vaccine could be applied to develop to EBV vaccine.

“A vaccine against EBV may result in the prevention of the majority of MS cases,” Munger says.