Biologists Discover Link: How Common Viruses May Trigger Multiple Sclerosis

For many years, common viruses, including Epstein-Barr, have been implicated in the development of multiple sclerosis (MS). MS is an autoimmune disease where the body’s immune system launches an attack on nerve cells in the brain and spinal cord. Recent findings reveal how this virus activates the immune response and how immunotherapy can mitigate recurrence and slow down disease progression.¹ This crucial research is detailed in Science Translational Medicine.

Emily Edwards, a rare disease researcher from Monash University in Melbourne, Australia, states that this discovery marks significant progress in understanding how the Epstein-Barr virus influences the onset of multiple sclerosis (MS).

The Epstein-Barr virus, a member of the herpesvirus family, is present in about 90% of the global population. For most individuals, the infection remains benign and does not lead to MS. However, as study co-author Natalia Dross of Massachusetts General Hospital notes, it is “well established” that this virus is a primary trigger for MS in certain individuals. Until now, the exact mechanisms by which the virus induces this condition were not fully understood.

In MS, immune cells target the protective myelin sheath surrounding nerves, leading to vision problems and difficulty in mobility. Approximately 2.9 million people worldwide are affected by this debilitating condition. While medication can slow disease progression and reduce the frequency and intensity of flare-ups, a cure remains elusive.

Immune System Response

Dross and her team aimed to investigate how different immune system components respond to the Epstein-Barr virus. They discovered that immune T cell activity was significantly higher in MS patients than in healthy individuals. Selectively depleting specific T cell types revealed that the depletion of CD4+ T cells dramatically lowered immune reactivity to the virus.⁺ This indicates that CD4+ T cells play a pivotal role in driving this response.

Dross further emphasizes the relevance of focusing on CD4+ T cells, especially given the promising results of a treatment drug called flexaliumab that targets CD4+ T cell activity to reduce inflammation and nerve damage. “This suggests a need to tailor our focus on this immune response,” she explains. Additionally, existing treatments known as anti-CD20 therapies have been found to lower the immune system’s response to the Epstein-Barr virus, although the mechanisms remain unclear.

To elucidate this, researchers measured CD4+ T cell levels in 60 MS patients before and six months after they commenced anti-CD20 treatment. Results showed that CD4+ T cell levels decreased approximately 2.5 times in the participants. These findings were validated in a second cohort, revealing that the reduction in T cell levels persisted for up to a year.

Moreover, participants receiving anti-CD20 treatment exhibited lower Epstein-Barr virus levels in their saliva compared to untreated MS patients and healthy individuals.

Edwards suggests that these results indicate the treatment effectively reduces viral activity in the body. Anti-CD20 therapy targets and eliminates infected B cells, thereby decreasing the stimuli for CD4+ T cells and leading to a diminished immune response. “This underscores the importance of these immune cell populations in disease exacerbation and highlights how immunotherapy may alleviate their effects and lessen disease severity,” Edwards added.