Epidemiological evidence implicates Epstein–Barr virus (EBV) as the cause of multiple sclerosis (MS). However, its biological role in the pathogenesis of MS is uncertain. The article provides an overview of the role of EBV in the pathogenesis of MS and makes a case for targeting EBV as a treatment strategy for MS.

EBV potentially triggers autoimmunity via molecular mimicry or immune dysregulation. Another hypothesis, supported by immunological and virological data, indicates that active EBV infection via latent-lytic infection cycling within the central nervous system or periphery drives MS disease activity. This supports testing small molecule anti-EBV agents targeting both latent and lytic infection, central nervous system-penetrant B-cell therapies and EBV-targeted immunotherapies in MS. Immunotherapies may include EBV-specific cytotoxic or chimeric antigen receptors T-cells, therapeutic EBV vaccines and immune reconstitution therapies to boost endogenous EBV-targeted cytotoxic T-cell responses.

EBV is the probable cause of MS and is likely to be driving MS disease activity via latent-lytic infection cycling. There is evidence that all licensed MS disease-modifying therapies target EBV, and there is a compelling case for testing other anti-EBV strategies as potential treatments for MS.