EBV latent and lytic genes uniquely contribute to Multiple Sclerosis development by various immunopathogenic mechanisms in susceptible hosts. Briefly, EBV infection shapes the B-cell repertoire and promotes the oligoclonal expansion and subsequent CNS infiltration of T-bet+CXCR3+ B cells, resulting in a cascade of immune dysregulation, CNS inflammation, and autoreactive T cell stimulation. Created in BioRender. Läderach, F. (2026) https://BioRender.com/b15duil.
ABSTRACT
Epstein–Barr virus (EBV) is a human tumor virus best known for its B cell-transforming capacity and association with lymphomas and carcinomas. Epidemiological studies have suggested that its infection, in addition, is necessary for the development of the autoimmune disease multiple sclerosis (MS). The very same oncogenes that drive EBV-associated malignancies might also induce differentiation of B cell subsets that initiate neuroinflammation. This review will discuss how insufficient immune control might allow for sizeable populations of T-bet+CXCR3+ B cells to infiltrate the central nervous system (CNS), attract other lymphocytes, efficiently stimulate T cells in the CNS, and differentiate into antibody-producing plasma cells, thereby contributing to inflammation and autoantibody production in a subset of MS patients. This CNS-infiltrating B-cell population could be targeted by EBV-specific treatments to complement existing MS therapies.