Host Genetic Architecture between Epstein–Barr Virus Activity and Multiple Sclerosis Reveals Shared Pathways, 2025, Yoshiaki Yasumizu et al

[Mij]

Abstract
Epstein–Barr virus (EBV) is strongly implicated as an essential environmental trigger of multiple sclerosis (MS), yet the host genetic mechanisms governing EBV activity and how infection triggers the disease are not known.

We developed a pipeline to quantify EBV DNA from whole-genome sequencing data and applied it to population-scale cohorts. Using this pipeline, we performed a cross-ancestry genome-wide association study (GWAS) of EBV DNA positivity in 617,186 individuals and identified 39 independent susceptibility risk loci, with the strongest associations in the HLA region. We validated this finding in our independent cohort (N=94) and found that quantitative PCR (qPCR)-confirmed EBV DNA positive individuals were enriched in the top decile of EBV polygenic risk scores (PRS) containing newly discovered loci.

A significant overlap with genetic variants associated with MS risk was observed. PRS and Mendelian randomization analyses further supported a causal role of EBV activity on MS risk, which was also seen in other autoimmune diseases. A meta-analysis of qPCR based case–control studies showed elevated EBV DNA positivity in MS. By establishing a single-cell RNA-seq method optimized for EBV detection, we identified EBV-infected B cells, primarily in memory B cells, atypical B cells and antibody-secreting cells from MS and healthy individuals.

Notably, EBV-infected memory B cells and atypical B cells showed strong upregulation of cytokines and costimulatory signals that influence T cell activation, IFNg secreting Tregs, and regulators of B cell differentiation and survival. EBV-infected memory B cells also upregulated risk genes from both the EBV and MS GWAS, suggesting that EBV-infected B cells constitute a critical hub that modulates T cell responses while simultaneously activating MS susceptibility pathways within the B cell compartment.

Together, these findings define a genetic and cellular framework linking EBV infection to the initiation of MS.
LINK

 

[Utsikt]

Notably, EBV-infected memory B cells and atypical B cells showed strong upregulation of cytokines and costimulatory signals that influence T cell activation, IFNg secreting Tregs, and regulators of B cell differentiation and survival. EBV-infected memory B cells also upregulated risk genes from both the EBV and MS GWAS, suggesting that EBV-infected B cells constitute a critical hub that modulates T cell responses while simultaneously activating MS susceptibility pathways within the B cell compartment.

@Jonathan Edwards would this be in line with your MS is drive by B-cells-hypothesis?

 

[Jonathan Edwards]

@Jonathan Edwards would this be in line with your MS is drive by B-cells-hypothesis?

It doesn't really link to my own speculations. I have suggested that certain B cells get into CNS and expand in MS in ways that they wouldn't normally. T cells would come along secondarily. That may be wrong but it doesn't particular imply abnormal interactions with T cells. People will always emphasise that though.

 

[Snoopydog1]

Merged thread

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Huge study reveals how Epstein-Barr virus may cause multiple sclerosis

The Epstein-Barr virus seems to affect gene expression and cell signalling in a way that causes the autoimmune condition multiple sclerosis

www.newscientist.com

I saw this headline in the News app a few days ago but couldn't see this posted anywhere here. Not being a scientist I don't know if the findings have implications for ME/CFS but it seems to explain how the epstein barr virus can cause multiple sclerosis in some people.

Unfortunately the link above only gives the abstract whereas the article I read was in full. I will try and see if I can find it but meanwhile will post the link.

 

[Snoopydog1]

I have found the full article which was quoted in Apple News on my iphone but not sure if I can post it here. Will look into this further.

Edited to say it isn't compatible with my laptop unfortunately.

 

[Felis Catus]

Unfortunately the link above only gives the abstract whereas the article I read was in full. I will try and see if I can find it but meanwhile will post the link.

Don't worry, here's a link to the full article: https://archive.ph/mICYx

 

[Mij]

Here is a reference link from the link Felis Catus posted above.

A Genetically Driven Immunologic Mechanism Underlying the Link between EBV and MS

Abstract​

Epstein–Barr virus (EBV) is implicated as a trigger of multiple sclerosis (MS), yet the host genetic mechanisms linking EBV activity to MS is unknown. We performed a cross-ancestry genome-wide association study of EBV DNA positivity (N=617,186), identifying 39 susceptibility risk loci that significantly overlapped with MS risk genes (p=1.3×10-12). Using our single-cell method for EBV detection, we identified 1,069 EBV-infected B cells across 38 individuals. EBV was predominantly in the latent phase and B cell receptor analysis revealed that memory B cell differentiation is altered by infection. Notably, EBV-infected switched memory and atypical B cells upregulated cytokines and costimulatory signals that influence T cell activation, and B cell signaling pathway. Finally, EBV-infected memory B cells upregulated risk genes from both the EBV and MS, suggesting that EBV-infected B cells link T cell modulation to activation of MS susceptibility pathways. These findings define a genetically driven immunologic mechanism underlying MS.