Multiple sclerosis (MS) is a chronic autoimmune disorder that attacks the central nervous system. For years, Epstein-Barr virus (EBV) has been strongly linked to MS, as nearly every person diagnosed with the condition shows evidence of past EBV infection. For example, a 2022 study analyzed millions of U.S. military recruits and found that getting infected with EBV increased a person’s risk of developing MS 32-fold.
But exactly how EBV is linked to the abnormal immune response seen in MS has remained unclear until now.
In a study published in Science Translational Medicine, scientists describe a new immune mechanism that could explain how EBV contributes to MS.
EBV is a very common herpesvirus that infects most people. However, only a small minority will go on to develop MS, with an estimated 2.9 million people worldwide living with the disease.
In MS, immune cells mistakenly attack the myelin sheath, the protective coating around nerves in the brain and spinal cord. This makes it difficult for the brain to send signals to the rest of the body, leading to problems such as muscle weakness, extreme fatigue and difficulty with balance.
Investigating the immune system
To discover which parts of the immune system respond to the virus, researchers compared blood samples from people with untreated MS, people receiving MS therapies and healthy volunteers. In the lab, they exposed blood cells to various proteins from different stages of the virus’s life cycle, as well as to individual viral proteins.
The researchers discovered that people with untreated MS have about twice the CD4+ T-cell response to EBV’s active, late-stage virus-particle proteins as healthy volunteers. They write in their paper, “Our results establish preferential CD4+ T cell reactivity to EBV late lytic antigens as a key feature of MS.”
CD4+ T cells, also known as helper T cells, coordinate the body’s inflammatory response. Specifically, these T cells respond most strongly to proteins that make up newly formed EBV viral particles, including parts of the virus’s outer shell. The researchers say this heightened immune response could help explain how EBV contributes to MS, although exactly how these T cells go on to damage myelin is unclear.
This overreaction occurred only with EBV. When the researchers looked at how participants reacted to two other common herpesviruses, both healthy volunteers and people with MS showed similar immune responses.
Current treatments
The study authors also tracked what happened to the CD4+ T-cell immune response when patients started common MS treatments. They studied people before and after starting anti-CD20 therapies, which deplete B cells. These are the immune cells in which the virus hides after infecting a person.
After starting therapy, patients had a 2.5-fold decrease in these overreactive CD4+ T-cell responses.
“Together, our findings establish EBV viral particle antigens as the dominant targets of CD4+ T cell responses in MS and demonstrate that these responses are modifiable by current therapies.” https://phys.org/news/2026-07-nanoparticles-immune-molecules-blood.html
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