Researchers at the University of Zurich have identified how the Epstein-Barr virus (EBV) interacts with a specific gene variant to contribute to the development of multiple sclerosis (MS). Their findings suggest that both environmental and genetic risk factors must work together for the disease to be triggered.
The study, led by Roland Martin from the Institute of Experimental Immunology at the University of Zurich, involved collaborations with scientists in Hefei, China, as well as researchers from the University of Tübingen and Imperial College London. The research highlights that while nearly everyone with MS has been previously infected with EBV, about 95 percent of healthy individuals also carry the virus. Therefore, infection alone is not enough for MS to develop.
If EBV infection occurs during late adolescence and results in infectious mononucleosis ("mono"), it can lead to a strong immune response that increases MS risk. The research focused on HLA molecules—receptors important for white blood cells in fighting viruses and involved in MS. With the presence of HLA-DR15 molecules, T cells recognize parts of EBV. The virus also remains in B cells for life.
"Both the T cells and the antibodies produced by B cells normally control the infection very effectively and prevent the virus from reactivating," says Martin.
In some cases, these immune cells mistakenly target brain cell structures as well as viral components. This autoimmune reaction plays a direct role in MS. According to researchers, EBV changes gene activity patterns within infected B cells, prompting them to produce myelin protein—a main target in MS.
Fragments of this myelin protein are then displayed on infected B cell surfaces along with HLA-DR15 molecules. T cells recognize these fragments and become activated, leading them to attack myelin sheaths surrounding nerve fibers in the brain and spinal cord. Damage to this protective sheath disrupts nerve signal transmission and leads to symptoms such as paralysis, vision problems or fatigue.
"Our study shows how the most important environmental and genetic risk factors can contribute to MS and trigger an autoimmune response that targets myelin components in the brain," Martin says.
Currently, several research groups along with biotech and pharmaceutical companies are working on vaccines against EBV because it is implicated not only in MS but also other autoimmune diseases like rheumatoid arthritis and systemic lupus as well as certain cancers. "Our findings reveal mechanisms that could be targeted by new therapies," Martin notes.
