Epstein-Barr virus and multiple sclerosis: Mechanisms, therapeutic implications, and emerging interventions

Multiple sclerosis (MS) is a neuroinflammatory disease shaped by genetic and environmental factors, with Epstein-Barr virus (EBV) emerging as the strongest environmental risk. Here, we review current evidence for the involvement of EBV in MS, its impact on existing therapeutics, and strategies for novel therapeutic directions. Compelling evidence indicates EBV infection precedes MS onset, likely contributing to disease initiation, relapses, and possibly progression through mechanisms such as molecular mimicry, B cell immortalization, and viral reactivation. Current MS therapies may indirectly suppress EBV by depleting B cells or restricting lymphocyte CNS entry. Novel strategies, including CAR-T/-NK cells, adoptive T cells, "kick and kill" approaches, and vaccines, aim to directly target EBV and offer promising new avenues for MS therapy.