Epstein-Barr Virus May Help Spark Multiple Sclerosis, Study Finds

A research team has uncovered a detailed chain of events showing how Epstein-Barr virus, or EBV, can help set off early multiple sclerosis (MS)-like damage in the brain. The findings, published in the journal Cell, offer a concrete biological explanation for one possible starting point of the disease.

The work, led by Nicholas Sanderson and Tobias Derfuss from the Department of Biomedicine at the University of Basel and University Hospital Basel, focuses on B cells. These immune cells are best known for making antibodies, but they also play a central role in many autoimmune diseases, in which the immune system mistakenly attacks the body’s own tissues.

In MS, the immune system targets myelin, the fatty insulating layer that wraps nerve fibers in the brain and spinal cord. Damage to myelin disrupts electrical signaling in the nervous system and can lead to symptoms such as vision problems, muscle weakness, and difficulty with balance and coordination.

For years, scientists have suspected that EBV, a virus that infects B cells and causes mononucleosis, is linked to MS. Almost everyone is infected with EBV at some point, usually in childhood, yet only a small fraction of people ever develop MS. That gap has been a major puzzle.

The connection between EBV and MS has long been unclear, according to Derfuss, a research group leader and senior author of the paper.

“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,” he said in a news release.

The new study zooms in on a rare but critical situation: what happens when EBV-infected B cells enter the brain and encounter myelin.

Under normal conditions, many people carry B cells that are potentially self-reactive, meaning they can recognize the body’s own proteins. That alone is not necessarily dangerous. The immune system has strict safety checks designed to eliminate or silence these risky cells if they become activated.

One of those checks involves signals that B cells must receive from other immune cells before they are fully activated. Without the right combination of signals, self-reactive B cells are usually shut down or removed.

The Basel team found that EBV can disrupt this balance. A viral protein produced by EBV mimics a crucial signal that acts like an “approval” step for B cells. With that signal faked by the virus, self-reactive B cells can slip past the usual safeguards and survive when they should be eliminated.

The brain is especially vulnerable to this kind of failure. During infections or inflammation, B cells can temporarily cross into brain tissue. Most of the time, they come and go without causing lasting harm. But if EBV-infected, self-reactive B cells enter the brain at the wrong moment, in the wrong place, the virus’s interference with immune control can have serious consequences.

In experimental mouse models, the researchers showed that these surviving B cells can capture myelin components in the central nervous system and trigger local damage. The resulting lesions closely resembled early MS plaques, but they did not arise from a massive, body-wide immune attack. Instead, they formed locally in the brain, driven by a specific sequence of events involving EBV and B cells.

Until now, B cells in MS were often thought to act mainly behind the scenes, influencing other immune cells that do the actual damage. The new work suggests B cells may also play a direct role in the earliest stages of lesion formation, right where the damage begins.

“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,” added Sanderson.

The team’s results offer a straightforward explanation.

“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,” Sanderson added.

Importantly, the researchers stress that this is not a single-cause story. MS is a complex disease shaped by genetics, environment, infections and other immune factors. The new study describes one initiating pathway that may help explain how the disease can begin long before any symptoms appear.

By pinpointing a specific mechanism at the very start of MS-like damage, the research shifts attention to the earliest moments when disease risk might still be altered. It highlights how timing, location and a person’s immune history can determine whether a brief immune disturbance leaves no trace or instead becomes the first spark of chronic brain inflammation.

This perspective could influence how scientists think about both treatment and prevention. Current MS therapies that target B cells are already among the most effective options for controlling established disease. The new findings help explain why shutting down B cells can work so well and suggest that intervening even earlier might be possible.

One long-term idea is to design vaccines that prevent severe EBV infections or change how the immune system responds to the virus. If EBV’s ability to mimic key immune signals is a crucial step in allowing dangerous B cells into the brain, then blocking that step could reduce the chance that MS ever gets started.

For now, the study offers a clearer picture of how a common virus and a rare immune misfire can intersect in a highly sensitive organ. By tracing that path in detail, the Basel team has opened new avenues for understanding, and eventually preventing, a disease that often begins silently years before it is diagnosed.

Source: University of Basel