How Epstein-Barr virus could trigger multiple sclerosis

Researchers at the University of California San Francisco have identified a new piece of evidence that helps explain how the Epstein-Barr virus could contribute to multiple sclerosis, a chronic autoimmune disease that affects nearly one million people in the United States.

The findings suggest that a specific group of immune cells may play a central role in linking the common virus to the neurological damage seen in MS. They also strengthen the case for drug discovery efforts aimed at Epstein-Barr virus, as researchers and companies explore antiviral and immune-based therapies for multiple sclerosis.

A long-suspected viral link

Epstein-Barr virus, or EBV, infects around 95 percent of adults worldwide and usually causes few lasting problems. However, scientists have known for several years that the virus is present in almost everyone who goes on to develop multiple sclerosis. 

Despite this strong association, the biological mechanism behind the connection has been unclear. The new study explains how the immune system’s response to EBV could help drive the disease.

“Looking at these understudied CD8+ T cells connects a lot of different dots and gives us a new window on how EBV is likely contributing to this disease,” said senior author Dr Joe Sabatino, MD, Assistant Professor of Neurology and a member of the UCSF Weill Institute for Neurosciences. 

Killer T cells under the spotlight

Multiple sclerosis develops when the immune system mistakenly attacks myelin, the protective coating that surrounds nerve fibres in the brain and spinal cord. This leads to inflammation and progressive neurological damage that can affect movement, vision and cognition.

Most MS research to date has focused on CD4+ T cells, which help coordinate immune responses but do not directly destroy cells. These cells are easier to study using animal models. Sabatino’s team instead turned their attention to CD8+ ‘killer’ T cells, which directly attack infected or damaged cells.

The researchers analysed blood and cerebrospinal fluid samples from 13 people with MS or early signs of the disease and five individuals without MS. They focused on CD8+ T cells that recognised specific proteins.

A striking imbalance in the nervous system

In participants without MS, these immune cells were found in similar numbers in the blood and cerebrospinal fluid. In contrast, people with MS showed a dramatic imbalance. The relevant CD8+ T cells were between 10 and 100 times more abundant in the cerebrospinal fluid than in the blood.

This sharp difference suggested that something unusual was happening within the central nervous system and that the immune cells were actively responding to it.

The researchers also detected Epstein-Barr virus in the cerebrospinal fluid of most participants, regardless of whether they had MS. Importantly, some viral genes were active and one of these was only active in people with MS. This points to a possible trigger for the excessive immune response that damages myelin.

Implications beyond multiple sclerosis

The findings add to a growing body of evidence linking EBV to autoimmune conditions. In addition to MS, the virus has been associated with lupus, rheumatoid arthritis and long COVID.

Some researchers are already testing treatments that specifically target EBV in people with MS. Sabatino believes this approach could have far-reaching benefits.

“The big hope here is that if we can interfere with EBV, we can have a big effect, not just on MS but on other disorders, and improve the quality of life for many, many people,” he said.

The research also provides important biological evidence that could help guide drug discovery. By clarifying how Epstein-Barr virus may drive immune damage in multiple sclerosis, the study could help to de-risk therapies that target the virus and accelerate the development of new treatments.