Researchers at the University of Basel and University Hospital Basel have found new evidence linking the Epstein-Barr virus (EBV) to early damage seen in multiple sclerosis (MS). The study, published in Cell, was led by Dr. Nicholas Sanderson and Professor Tobias Derfuss from the Department of Biomedicine.
While most people are infected with EBV early in life, only a small fraction develop MS. The research team focused on B cells, immune cells that can sometimes react against the body's own proteins. Normally, these self-reactive B cells are removed by safety mechanisms before they can cause harm.
However, the brain is particularly sensitive. During infections or inflammation, B cells may enter brain tissue. Usually this does not lead to lasting problems, but under certain rare conditions, the usual safety checks can fail.
The study shows that EBV can disrupt how B cells are controlled. A viral protein mimics a signal needed for B cell survival, allowing self-reactive B cells to persist when they should be eliminated. In mouse models, these surviving B cells caused local damage to myelin—the protective covering around nerve fibers—similar to early MS lesions.
"The role of EBV in MS has been quite mysterious for a long time. We have identified a series of events including EBV infection that has to happen in a clearly defined sequence to cause localized inflammation in the brain. While this is not fully explaining all aspects of MS, it might be the spark that ignites chronic inflammation in the brain," said Tobias Derfuss.
Previously, scientists thought B cells contributed to MS mainly through indirect effects on other immune cells. This research suggests that B cells could play a direct role at the earliest stages of lesion formation. The findings help connect several known features of MS: its association with EBV infection, involvement of B cells, and why treatments targeting these cells are effective.
"This is not a single-cause explanation for MS," said the researchers. "Instead, it describes one initiating pathway that could help explain why the disease begins—long before symptoms appear."
Nicholas Sanderson explained: "Experts in the field mostly agree that both B cells and Epstein-Barr virus are somehow involved in the disease, but there is no consensus about how. The model that emerges from the work of our team is very simple and therefore very persuasive. In a nutshell, we suggest that virus-infected B cells cause the lesions."
The study highlights how timing and specific conditions can determine whether immune-related damage occurs in the brain at all. Researchers hope this understanding will inform future prevention strategies for MS—for example by developing vaccines against severe EBV infections to limit risky immune responses.
