New Studies Shed Light on How Epstein-Barr Virus Triggers Multiple Sclerosis
Two new studies clarify how Epstein-Barr virus may trigger multiple sclerosis: one shows a doubled CD4+ T cell response in untreated patients, while another reveals EBV-activated B cells cause brain inflammation in mice. Insights point to potential therapies targeting EBV-specific immune activity.
Researchers are gaining deeper insight into how Epstein-Barr virus (EBV) contributes to multiple sclerosis (MS), with two studies revealing distinct immune cell responses that could inform new therapies. While EBV infects over 95% of adults globally, fewer than 1% develop MS, and research now points to specific T cell and B cell activity driving the disease.
A study published July 15 in Science Translational Medicine found that people with untreated MS mount a doubled immune response to EBV, characterized by increased activity among CD4+ T cells—a type of immune cell that triggers inflammation. The analysis compared blood samples from healthy individuals, untreated MS patients, and those receiving MS therapies. Common MS treatments significantly decreased EBV-specific CD4+ T cells and eliminated EBV in saliva. The researchers concluded that preferential CD4+ T cell reactivity to EBV is a key feature of MS, providing a framework for developing EBV-targeted therapies, including vaccines and antivirals.
In separate experiments, scientists using lab mice with a human-like immune system observed that after EBV infection, B cells became unusually active and traveled to the brain. There, they released signals that attracted T cells, and together these immune cells caused inflammation and early brain damage mimicking the early stages of MS. When the researchers used a drug to remove B cells, there were far fewer T cells in the brain and much less immune activation. The findings suggest EBV may set MS in motion by altering B cell behavior, which in turn draws T cells to the central nervous system.
The idea that the immune system's response to EBV cross-reacts with myelin—the protective coating around nerve fibers damaged in MS—is a leading explanation for how the virus contributes to the disease. Other factors such as genetics, sex, smoking, obesity, and low vitamin D are known to influence MS risk, but EBV is considered a necessary trigger. Previous Harvard-led research showed EBV increases the risk of developing MS by 32-fold.
Current MS treatments largely suppress the immune system to reduce relapses and slow progression. Some of the most effective therapies target B cells using monoclonal antibodies such as ocrelizumab, rituximab, and ofatumumab, which lower B cell numbers and may reduce the pool of EBV-infected cells. While these drugs improve outcomes, they can increase infection risk and impair vaccine responses. The new insights into EBV-specific immune responses could motivate development of more targeted treatments and EBV vaccines, though none are currently approved.