Abstract
The cause of multiple sclerosis (MS) has eluded medical science for over a century. Pierre Marie speculated that MS is an infectious disease and this paradigm has had a prominent place in the discussion. A number of candidate pathogens have been proposed, but most have not survived scrutiny. In this review, we summarize the evidence that MS is caused by Epstein-Barr virus (EBV), which has been a prominent candidate for several decades. Although there is much suggestive evidence that EBV is involved in the pathogenesis of MS, the precise effect of EBV is still unclear. EBV is more common in MS patients than in controls. A history of infectious mononucleosis, and high baseline EBV antibody titers are risk factors for MS. More controversial are findings of changes in the reactivity of the T-cell repertoire, presence of EBV antibodies in the cerebrospinal fluid, and presence of EBV in meningeal lymphoid follicles and perivenular infiltrates in the white matter. The contribution of EBV to the cause of MS is not yet established, but a relationship is clearly present.
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