Epstein-Barr virus together with a gene variant contributes to onset of multiple sclerosis

One of the leading triggers for multiple sclerosis (MS) is an infection with the Epstein-Barr virus. However, certain gene variants also play an important role. Researchers at the University of Zurich have now shown that it is the molecular interaction between environmental and genetic risk factors that ultimately triggers the disease.

Recent findings suggest that the Epstein-Barr virus (EBV) is involved in both causing multiple sclerosis (MS) and shaping its progression. Everyone who has MS has previously been infected with EBV, and around 95 percent of healthy people also carry it. Infection with this common herpes virus alone is therefore not sufficient for the disease to develop. If EBV is acquired in late adolescence and becomes symptomatic – a condition known as infectious mononucleosis, or mono – it triggers a particularly strong immune response that significantly increases the risk of developing MS.

A research team at the Institute of Experimental Immunology at the University of Zurich (UZH) has now presented new findings that show how the Epstein-Barr virus, together with a gene variant typical of MS, contributes to the onset of the disease. The research, led by Roland Martin, was conducted in collaboration with scientists in Hefei (China), the University of Tübingen and Imperial College London.

Two types of immune cells drive autoimmune response in MS

In addition to EBV infection, genetic risk factors also play a role – in particular the so-called HLA-DR15 haplotype."

Roland Martin, University of Zurich

HLA molecules act as receptors for certain white blood cells that play a key part in the defense against viruses and in MS. Together with the HLA-DR15 molecule, T cells recognize components of the Epstein-Barr virus. The virus also infects B cells, another group of immune cells, where it persists 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.

However, alongside this protective role, both types of immune cells sometimes recognize not only virus components, but also the body's own brain cell structures. As a result, both of these cells are also directly involved in the autoimmune reaction in MS. EBV changes the pattern of activated genes in infected B cells, which makes them produce a myelin protein that is a key target structure in MS.

Body's own structures activate immune cells

Fragments of this protein are presented on the surface of infected B cells together with the HLA-DR15 molecule and are recognized by T cells. The activated immune cells then go on to attack the myelin sheath of nerve cells in the brain and spinal cord. Progressive damage to this sheath, which acts as a protective layer that envelops nerve fibers and enables nerve cells to transmit signals efficiently, leads to a wide range of neurological symptoms such as paralysis, visual impairment 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. A number of research groups, biotech and pharmaceutical companies are currently working on vaccines against EBV. The virus not only plays a major role in MS but is also a factor in other autoimmune diseases such as rheumatoid arthritis and systemic lupus, and can cause a number of cancers. "Our findings reveal mechanisms that could be targeted by new therapies," Martin notes.