Epstein-Barr virus reactivation may trigger MS flares, study shows
Discovery could provide new insights into disease cause
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Epstein-Barr virus is a risk factor for MS. (Image by iStock)
- Reactivation of the dormant Epstein-Barr virus in immune cells can trigger disease flares in multiple sclerosis.
- This reactivation is detectable in the weeks and months leading up to an active relapse.
- Findings highlight a potential new path for developing targeted therapeutics specifically against the virus.
Reactivation of dormant Epstein-Barr virus (EBV) in immune cells may trigger disease flares in multiple sclerosis (MS), a study showed. The researchers found that EBV reactivation in immune cells is detectable in the weeks and months before an MS relapse.
“We believe this work provides foundational insights into the cause of multiple sclerosis,” study co-author Tanuja Chitnis, MD, chief of the neuroimmunology division at Mass General Brigham, said in a news story from the hospital. “This study puts all the pieces together, showing a timeline of how the reactivated virus interacts with risk genes to unleash inflammation before relapse occurs.”
The researchers noted that their study doesn’t definitively prove a cause-and-effect relationship between EBV reactivation and MS relapse. It was limited to a relatively small number of patients, so further research is necessary to validate the results. Still, the scientists are optimistic that their findings may help shed light on the biological underpinnings of MS and provide avenues for new treatments.
“These findings open a whole new avenue for targeted therapeutics,” Chitnis said. “Currently, most MS treatments work by broadly suppressing the immune system. Our results suggest there’s an opportunity to be more precise and develop approaches that target EBV or the immune cells involved in relapse.”
The study, “EBV reactivation priming of the peripheral immune system in multiple sclerosis relapse,” was published in Nature Medicine.
Understanding what leads to a relapse
MS is an autoimmune disease marked by inflammation that damages healthy cells in the brain and spinal cord. In most patients, MS is characterized by relapses or flares, periods in which MS symptoms suddenly worsen due to new or intensifying inflammation.
The causes of MS are not fully understood, but several risk factors have been identified, including genetic disposition and EBV infection. The virus is best known for causing infectious mononucleosis, but it also causes nonspecific childhood illness.
Most people have been infected with EBV by the time they reach adulthood, but a small number go on to develop MS, for reasons that are unknown. After the virus infects the body, it lingers in a dormant state in B-cells, immune cells known to be involved in MS.
The researchers wanted to better understand what happens in the immune system right before an MS relapse. They analyzed immune cells in blood samples from 114 people with MS and 21 healthy participants during a decades-long study, the Comprehensive Longitudinal Investigation of Multiple Sclerosis.
The scientists found that B-cells show notable changes in activity just before an MS relapse. Data suggested that dormant EBV in infected B-cells reactivates in the weeks and months prior to an MS relapse. At the same time, there is an increase in the number of ABC-like B-cells, a subset linked to chronic infection and autoimmune disease. These ABC-like B-cells were also found to have increased activity of MS risk genes prior to relapse.
ABC-like B-cells can move into the brain with relative ease, so they are a likely suspect as the instigator linking EBV reactivation in circulating B-cells to new MS activity in the nervous system.
Based on these findings, the researchers proposed a model in which environmental factors trigger EBV reactivation in B-cells and EBV-associated genetic changes result in the preferential survival of ABC B-cells enriched for MS risk genes.
“These data support a model in which episodic [reactivation of EBV in B-cells] … precedes relapse by weeks to months and is accompanied by expansion of ABC-like B cells and [body-wide inflammatory cell profiles] that, within a permissive genetic background, increases the likelihood of relapse,” they wrote.
While the model requires validation, the team noted that if it holds true, EBV isn’t just a key MS risk factor — the virus also drives disease activity, carrying important implications for potential treatments.
“Our findings extend the role of EBV in MS beyond the requirement of initial infection for disease onset to episodic reactivation as a candidate driver of relapse biology,” the scientists concluded.
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