Epstein-Barr virus may be the initial trigger for MS

Epstein-Barr virus (EBV) may be the first trigger for the development of multiple sclerosis (MS) in most cases, says an expert.

In a study, the risk of MS increased to 32-fold after EBV infection. [Science 2022;doi:10.1126/science.abj8222]

“We’ve always known that MS is an autoimmune disease of unknown aetiology,” said principal investigator Dr Alberto Ascherio from the Harvard T. H. Chan School of Public Health, and professor of medicine, Harvard Medical School in Boston, Massachusetts, US. “Now we’ve found that MS is a complication of a viral infection. We can now redirect research to find antiviral drugs for the disease.”

The top putative causal agent

MS is a chronic inflammatory demyelinating disease of the central nervous system. EBV, a human herpesvirus, is a top candidate among the putative causal agents.

Researchers tested the hypothesis that EBV causes MS in a cohort of 10 million young adults on active military duty in the US, 955 of whom were diagnosed with MS during their service period. Stored blood samples were used to determine the link between EBV infection and MS over a 20-year period from 1993 to 2013.

Overall, 801 MS case-patients were evaluated vs 1,566 matched controls without MS. While the risk of MS increased after infection with EBV, this was not seen after infection with the cytomegalovirus, a herpes virus that, like EBV, is transmitted through the saliva. 

One of the 801 MS case-patients had no serologic evidence of EBV. The hazard ratio (HR) for MS between EBV seroconversion and persistent EBV seronegative was 32.4 (p< 0.001).

There were no signs of neuroaxonal degeneration before EBV seroconversion in individuals who later developed MS when serum concentrations of neurofilament light chain (sNflL), a biomarker of neuroaxonal degeneration, were measured in samples from EBV-negative individuals.

“This suggests that EBV infection preceded not only the symptom onset but also the time of the first detectable pathological mechanisms underlying MS,” Ascherio pointed out. “The increased MS risk observed with  EBV almost completely rules out confounding by known risk factors.”

While smoking and vitamin D deficiency doubled the risk of MS, genetic disposition and childhood obesity only raised the risk to a moderate degree. It was not clear however why only some people infected with EBV went on to develop MS, Ascherio said.

Vaccines & antivirals

But as most MS cases appear to be caused by EBV, a suitable vaccine might help to prevent the disease. “A vaccine could, in theory, prevent infection and prevent MS,” said Ascherio. “Antivirals that target EBV early in the course of the disease may also be an effective therapy.”

“Infection with EBV is the initial pathogenic step in MS, but additional fuses must be ignited for the full pathophysiology,” said Dr William Robinson from the Division of Immunology and Rheumatology, Department of Medicine, Stanford University in Stanford, California, US. “Now that the initial trigger for MS has been identified, perhaps MS could be eradicated.” [Science 2022;doi:10.1126/science.abm7930]