A new study lends much support to the link between Epstein-Barr Virus (EBV) and multiple sclerosis (MS). Using data from more than ten million United States military recruits monitored over a 20-year period, 955 of whom were diagnosed with MS during their service, lead author Kjetil Bjornevik and colleagues tested the hypothesis that MS is caused by EBV. They found that the risk of developing MS in individuals who were EBV-negative increased by 32-fold following infection with the virus. Based on their study and other research, there are clearly other factors involved in the development of the disease, but the link to EBV stands out.
“These findings,” say the authors, “cannot be explained by any known risk factor and suggest EBV as the leading cause of MS.”
MS is a progressive neurologic disease that affects 2.8 million people worldwide and for which there is no definitive cure.
The Harvard T.H. Chan School of Public Health researchers’ findings were published online in Science January 13, 2022.
“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,” said Alberto Ascherio, professor of epidemiology and nutrition at Harvard Chan School and senior author of the study. “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.”
EBV is a herpes virus that can cause infectious mononucleosis and establishes a latent, lifelong infection of the host. Proving a causal relationship between the virus and the disease has been difficult because EBV infects approximately 95% of adults, MS is a relatively rare disease, and the onset of MS symptoms begins about 10 years after EBV infection.
To determine the connection between EBV and MS, the Chan School researchers conducted a study among more than 10 million young adults on active duty in the U.S. military and identified 955 who were diagnosed with MS during their period of service.
The team analyzed serum samples taken biennially by the military and determined the soldiers’ EBV status at time of first sample and the relationship between EBV infection and MS onset during the period of active duty. In this cohort, the risk of MS increased 32-fold after infection with EBV but was unchanged after infection with other viruses. Serum levels of neurofilament light chain, a biomarker of the nerve degeneration typical in MS, increased only after EBV infection. The findings cannot be explained by any known risk factor for MS and suggest EBV as the leading cause of MS.
Ascherio says that 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.
“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,” said Ascherio.
The researchers note that one of the most effective treatments for MS is anti-CD20 monoclonal antibodies, which have to be administered by intravenous infusion and may increase the risk of infections. Directly targeting EBV could have major advantages compared with anti-CD20-based therapies, they say.