A University of Zurich-led team has uncovered how a common virus and a specific genetic variant can jointly spark multiple sclerosis. The work helps explain who gets MS and points toward new ways to prevent or treat the disease.
A common virus carried by most people worldwide may help trigger multiple sclerosis only when it collides with a specific genetic risk factor, according to new research conducted by the University of Zurich in collaboration with scientists from University of Science and Technology of China, the University of Tübingen and Imperial College London.
Published in the journal Cell, the study sheds light on a long-standing mystery: why infection with Epstein-Barr virus, or EBV, appears to be necessary for MS to develop, yet is not enough on its own to cause the disease.
Nearly everyone with MS has been infected with EBV, a herpes virus best known for causing infectious mononucleosis, or mono, when caught in late adolescence. But about 95% of healthy adults also carry the virus without ever developing MS.
The new work, led by Roland Martin at the University of Zurich’s Institute of Experimental Immunology, helps explain that gap by showing how EBV and a particular gene variant can work together at the molecular level to launch an autoimmune attack on the brain.
The research team focused on a genetic pattern called HLA-DR15, which is strongly associated with MS. HLA molecules sit on the surface of cells and act like display stands, showing fragments of proteins to white blood cells so the immune system can tell friend from foe.
“In addition to EBV infection, genetic risk factors also play a role – in particular the so-called HLA-DR15 haplotype,” Martin said in a news release.
In people who carry HLA-DR15, the team found, EBV infection sets off a chain reaction involving two key types of immune cells: T cells and B cells.
T cells are white blood cells that patrol the body looking for infected or abnormal cells. B cells produce antibodies and can be infected by EBV, which then persists in them for life. Under normal circumstances, these cells keep the virus in check.
“Both the T cells and the antibodies produced by B cells normally control the infection very effectively and prevent the virus from reactivating,” Martin added.
The new study shows that in some people with the HLA-DR15 variant, EBV infection subtly rewires infected B cells. The virus changes which genes are switched on inside these cells, pushing them to produce a myelin protein that is a prime target in MS.
Myelin is the fatty, insulating sheath that wraps around nerve fibers in the brain and spinal cord. It allows electrical signals to travel quickly and efficiently. When myelin is damaged, nerve communication slows or fails, leading to symptoms such as muscle weakness, paralysis, vision problems and severe fatigue.
According to the researchers, fragments of the myelin protein made by EBV-infected B cells are carried to the cell surface and displayed together with the HLA-DR15 molecule. T cells that are tuned to recognize this combination become activated. Once activated, they can mistakenly attack the body’s own myelin in the brain and spinal cord, turning a normal antiviral response into a self-directed, or autoimmune, assault.
In other words, the same immune cells that usually protect against EBV can, in the wrong genetic and viral context, be redirected against the nervous system.
“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,” added Martin.
Multiple sclerosis is a chronic, often disabling disease that typically begins in young adulthood and affects hundreds of thousands of people worldwide. Scientists have long suspected that both genes and environment are involved, but the precise mechanisms linking them have been difficult to pin down. EBV has emerged as a leading environmental suspect, especially when infection occurs later in life and causes mono, which is associated with a sharply increased risk of MS.
By mapping how EBV and HLA-DR15 interact inside immune cells, the new research provides a clearer picture of how that risk may be translated into disease.
The findings also arrive at a time when several research groups, biotech firms and pharmaceutical companies are racing to develop vaccines against EBV. Because the virus is implicated not only in MS but also in other autoimmune diseases such as rheumatoid arthritis and systemic lupus, as well as in certain cancers, an effective vaccine could have wide-ranging benefits.
Beyond vaccines, the study points to more targeted treatment strategies. If scientists can block the specific steps that lead EBV-infected B cells to present myelin fragments to T cells, they may be able to prevent or dampen the autoimmune response without shutting down the entire immune system.
“Our findings reveal mechanisms that could be targeted by new therapies,” Martin added.
Future work will likely explore how common the risky combination of EBV-driven changes and HLA-DR15 is among people with MS, and whether similar mechanisms are at play in other autoimmune conditions linked to EBV. For patients and clinicians, the research offers a more concrete explanation of how a ubiquitous virus and inherited genes can intersect to produce a life-altering disease — and a clearer roadmap for interventions that might one day stop MS before it starts.
Source: University of Zurich