The role of Epstein-Barr virus in multiple sclerosis: From pathogenesis to therapeutic potential

A growing body of evidence positions Epstein-Barr virus (EBV) as a central agent in the etiopathogenesis of multiple sclerosis (MS). Compelling epidemiological studies now demonstrate that EBV infection precedes MS onset and is a necessary precondition for disease development. This is supported by pathology findings revealing EBV-infected B cells within CNS lesions and immunogenetic data linking viral and human genetic susceptibility to MS risk. Mechanistically, EBV appears to act as an upstream trigger that reshapes B cell function, promotes molecular mimicry with CNS antigens, and drives compartmentalized neuroinflammation. In this Review, we synthesize epidemiological, pathological, immunogenetic, and clinical-therapeutic evidence to construct a coherent model of EBV-driven MS pathogenesis. We examine how current MS therapies intersect with EBV biology and discuss the challenges and opportunities in developing EBV-targeted strategies, including vaccines and antivirals, for disease prevention and early intervention. Finally, we highlight key unresolved questions and outline a translational research agenda aimed at intercepting MS through virologically informed approaches.