Immune System “Misdirection” May Explain Link Between Epstein-Barr Virus and MS
EBVs link with MS is likely caused by cross-reactivity that leads the immune system to mistakenly attack nerve cells.
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Previous infection with the Epstein-Barr virus (EBV) has been associated with the onset of multiple sclerosis (MS), but how the infection might contribute to the development of the disease has not been clear.
Now, research from the University of Birmingham has found that following EBV infection there is more immune system cross-reactivity, where the body’s immune system binds to the wrong target, than previously thought. The findings were published in the journal PLOS Pathogens.
T cells that target viral EBV proteins also recognize brain proteins
MS is a chronic inflammatory disease of the central nervous system (CNS) that an estimated 2.8 million individuals suffer from.
In 2022, a study determined that EBV infection greatly increases the risk of subsequent MS, prompting a surge in studies looking to identify the mechanism behind how EBV infection contributes to MS.
What is EBV?
EBV is a herpesvirus that more than 90% of adults globally are infected with. Often, we contract the virus when we are young and there are no symptoms. Individuals who contract EBV as adults are much more likely to develop glandular fever, otherwise known as infectious mononucleosis. It was the first virus to be discovered that could cause human cancer and has since been implicated in the development of a range of different diseases, including in the development of MS.
In the present study, researchers investigated T-cell and antibody responses to EBV. They looked at blood samples from people with MS, as well as healthy people infected with EBV and people recovering from glandular fever caused by recent EBV infection.
The study found that T cells that target viral EBV proteins can also recognize brain proteins. These cross-reactive T cells can be found in people with MS but also in those without the disease. This suggests that differences in how these immune cells function may explain why some people get MS after EBV infection.
While previous research has shown that antibody responses to EBNA1 (an EBV protein) also recognize a small number of proteins of the CNS, the findings suggest that the human immune system cross-recognizes a much broader array of EBV and CNS proteins than previously thought.
A prominent theory is that the link between EBV and MS is not due to uncontrolled virus infection and the researchers suggest these findings give weight to this line of thinking. “This [research] strengthens the hypothesis that EBV’s role in development and progression of MS is extremely complex and multifaceted,” said the authors.
During blood testing, there was evidence that cross-reactive T cells that target EBV and CNS proteins are also present in many healthy individuals. The researchers suggest that it may be the ability of these cells to access the brain that is important in MS.
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Subscribe for FREEWhile identifying which proteins are important in MS may help provide targets for future personalized therapies, the researchers warn that “greater understanding is needed surrounding EBV’s role in CNS autoimmunity, and caution must be taken when designing future therapies for MS which target EBV such as vaccination or adoptive T-cell therapies.”
Reference: Thomas OG, Haigh TA, Croom-Carter D, et al. Heightened Epstein-Barr virus immunity and potential cross-reactivities in multiple sclerosis. PLoS Pathog. 2024;20(6):e1012177. doi: 10.1371/journal.ppat.1012177
This article is a rework of a press release. Material has been edited for length and content.
