Scientists uncover immune cell clues behind Epstein-Barr virus link to MS
New findings provide 'genetic framework' for advancing treatments
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New research has identified genes in specific immune cells behind multiple sclerosis risk and Epstein-Barr virus susceptibility. (Image from iStock)
- Researchers in China identified specific genes in immune cells that link multiple sclerosis risk to Epstein-Barr virus susceptibility.
- Gene activity changes in immune cells help explain how viral infections may trigger neurological inflammation.
- Future steps require rigorous cell and animal model validation before testing potential treatments in humans.
Scientists have identified dozens of genes in specific immune cells that may influence the risk of multiple sclerosis (MS) and susceptibility to Epstein-Barr virus (EBV), offering new clues about the biological mechanisms that may connect EBV infection with MS.
A new study by this research team, from two universities in China, also identified several existing compounds that interact with some of these genes, providing possible starting points for future research into MS and EBV, a member of the herpes virus family, and potentially laying the foundation for new treatments.
The researchers stressed that these computational analyses represent only a first step, noting that evaluation of these potential therapy candidates will “require rigorous stepwise validation in [cell models, computer-based testing], and animal models before progressing to human studies.”
Still, this work “provides a single-cell genetic framework for prioritizing immune-cell-specific candidate targets,” the team wrote.
The study, “Mapping the immune-genetic architecture of Epstein-Barr virus-related phenotypes and multiple sclerosis through a single-cell genetic framework for target prioritization and pharmacologic hypothesis generation,” was published in the journal Multiple Sclerosis and Related Disorders.
MS, an autoimmune disease, is marked by inflammation in the brain and spinal cord. Its causes aren’t fully understood, but several risk factors have been identified, including EBV infection.
Epstein-Barr is a common virus that causes infectious mononucleosis, commonly called mono, as well as other nonspecific childhood illnesses. Nearly everyone with MS has been infected with EBV, and research suggests that EBV infection is a key risk factor for developing MS. However, the mechanisms connecting EBV infection to MS remain unclear.
Some studies have suggested that EBV may interact with other risk factors. For example, people with specific genetic traits seem to experience changes in immune activity upon EBV infection that predispose them to MS. Still, the team noted that “clinical research directly targeting the post-EBV window to prevent future multiple sclerosis remains in its infancy.”
Exploring other pieces of the puzzle behind the MS, EBV link
To date, studies into the genetics of MS risk have usually focused on changes in the genetic code. But these changes are only one piece of the puzzle: Within cells, individual genes are constantly being switched on or off depending on what the cell is doing.
In this study, the scientists wanted to explore how changes in genetic activity within different types of immune cells may contribute to MS risk and EBV susceptibility.
Using genetic and gene-activity data from large databases, the team analyzed the activity of more than 14,000 genes across 14 types of immune cells. The scientists then used statistical methods to identify genes whose activity was associated with MS or infectious mononucleosis, which they used as their main measure of an EBV-related condition.
A total of 37 genes were identified as consistently associated with MS. For example, higher activity of the APOM gene in cells called classical monocytes was tied to a reduced MS risk, while higher activity of the PLEK gene in natural killer (NK) immune cells and certain T-cells was linked to increased MS risk.
These findings … [suggest] that [gene activity changes] within specific immune contexts may contribute to … inflammatory responses [in MS].
Some genes showed different associations depending on the immune cell involved: The researchers found, for example, that higher AHI1 activity was associated with a lower risk of MS in several immune cell types, including NK cells and some B-cells, but with a higher risk in a subset of T-cells.
The scientists also identified genes associated with EBV susceptibility. For instance, higher SERPINB1 activity in NK cells was associated with greater susceptibility to infection, whereas higher activity of HLA-G in certain B-cells and RNASET2 in NK cells was linked to lower susceptibility.
“These findings provide candidate immune-cell and pathway-level hypotheses for EBV-related biology and MS, suggesting that [gene activity changes] within specific immune contexts may contribute to altered antiviral surveillance or inflammatory responses,” the researchers wrote.
The researchers next used computational analyses to screen for compounds that could target any of the identified genes. They identified several potential compounds that may be used in future research. For example, a molecule called myristic acid may affect the APOMÂ gene in classical monocytes.
These computer-based findings provide a starting point for future research, the scientists concluded, noting that “these insights provide testable molecular entry points for future studies.” However, the team stressed that more work is needed to evaluate whether these compounds may provide benefit for people with MS.
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