From Mono to MS? How a Common Virus Can Set Off a Serious Disease
October 1, 2025
We’ve long known that the Epstein-Barr virus (EBV), the culprit behind infectious mononucleosis or “mono,” is nearly universal. Most people contract it at some point, and for the vast majority, it passes without major consequence. But for a small subset of individuals, EBV infection may trigger a much more serious disease: multiple sclerosis (MS).
In a recent study led by Neda Sattarnezhad Oskouei, MD, MS, Tobias Lanz, MD, and collaborators at Stanford University and in Sweden, researchers have uncovered more evidence tying EBV to MS, and zeroed in on the biological mechanisms that may explain this mysterious link. The work focuses on molecular mimicry, a phenomenon where the body’s immune response to a virus mistakenly targets its own tissue. In this case, the brain.
A Case of Mistaken Identity
“Molecular mimicry is basically the confusion of our immune system,” explained Lanz. “When our immune system encounters a virus, it produces antibodies to fight off the infection. But sometimes, parts of a virus can resemble proteins found in the human body.” The Stanford study found that a specific EBV protein, EBNA1, closely resembles a brain protein called GlialCAM, which plays an important role in supporting the myelin sheath, which is the protective coating that surrounds nerve fibers.
In people with MS, the immune system damages this sheath, leading to inflammation and neurological symptoms ranging from vision loss and fatigue to cognitive dysfunction. The researchers discovered that in some people, antibodies created to fight EBV accidentally cross-react with GlialCAM, meaning they not only attack the virus but also mistakenly target a similar-looking brain protein. This case of mistaken identity causes the immune system to attack the brain instead of just the virus, which could help explain how EBV sets the stage for MS.
The Genetic Connection
But EBV infection alone isn’t enough to cause MS. Nearly 95% of adults carry the virus, while MS remains a relatively rare disease. So why do only a few people go on to develop it?
The study points to genetics, specifically the HLA-DRB1*15:01 gene, as a key piece of the puzzle. This gene is already known to be the strongest inherited risk factor for MS. “The findings suggest that individuals with this gene are more likely to produce the harmful, cross-reactive antibodies that confuse EBNA1 with GlialCAM,” explains Sattarnezhad.
In fact, people who had both the HLA-DRB1*15:01 gene and high levels of these antibodies were up to nine times more likely to develop MS than those without either risk factor. This additive effect could eventually help identify people who are at higher risk, long before symptoms appear.
Beyond GlialCAM: A Broader Immune Reaction
The researchers didn’t stop with GlialCAM. They also studied how antibodies responded to other brain proteins, like CRYAB and ANO2, that also bear resemblance to EBV.
Many people with MS had immune responses to several of these proteins, showing that once the attack starts, it can spread to other areas of the brain.
This process, also known as “epitope spreading,” could help explain the progressive nature of MS and why early intervention is so critical.
What It Means for the Future
This research strengthens the case that EBV is not just correlated with MS — it may be a key causal factor. The findings offer a potential roadmap for identifying who is most at risk and could lay the foundation for preventative therapies.
“If we can block EBV or its downstream effects, we may be able to stop MS before it starts,” said Sattarnezhad.
Efforts are already underway to develop vaccines and antiviral therapies targeting EBV. Future work could explore whether treating EBV infection early, or preventing it altogether, can lower MS risk in genetically susceptible individuals.
While we don’t yet have a cure for MS, understanding how it begins is a critical step toward stopping it. This study brings us closer to that goal and offers new hope that one day, the path from mono to MS could be intercepted.