So far 233 common genome loci have been associated with disease risk and one variant associated with disease progression. The majority of these map to the immune system, targeting T cells, regulatory T cells, and, in particular, B cells. Here, they analyzed 617,186 participants applying harmonized viral-detection across 108 ancestries. They identified 39 susceptibility risk loc associated with EBV.
EBV-positive cells were predominantly detected among plasmablasts, followed by B memory and B intermediate cells (transitional cells), whereas
naïve B cells showed almost no EBV positivity. They suggest host genetic control of EBV activity is exerted primarily within the memory B-cell compartment rather than at the terminally differentiated plasmablast stage. Associations were found not only with MS but also other autoimmune conditions including Lupus and rheumatoid arthritis
“EBV–infected B cells are a key modulator of T cells and that MS susceptibility genes are preferentially activated within EBV infected B cells, defining a genetic and cellular framework linking EBV infection to MS and
potentially other autoimmune diseases”.
EBV-positive B cells showed elevated expression of receptors crucial for B-cell differentiation and survival…host genetic risk for MS and genetic determinants of EBV activity converge within EBV-infected memory B cells.
There you have it, who would have thought that our paper in 2017 would have a similar conclusion but is it is further icing on the “Christmas” cake. However it is all sold from the prospective of T cell activation
Go have a read of this unpublished/unreviewed paper.
Yasumizu Y, Kim N, Rivier CA, Moon J, Kojima S, Chen HL, Buitrago-Pocasangre N, Quinn E, Vaughn S, Morgan A, Huo S, Silberfeld A, Sumida TS, Ishigaki K, Longbrake EE, Falcone GJ, Hafler DA. Host Genetic Architecture between Epstein-Barr Virus Activity and Multiple Sclerosis Reveals Shared Pathways. medRxiv [Preprint]. 2025 Dec 15:2025.12.11.25342083.
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.
Source: multiple-sclerosis-research.org