Recent studies have revived interest in the long-scrutinized association between Epstein-Barr virus (EBV) and multiple sclerosis (MS). We review this evidence and discuss it in relation to MS pathological and clinical features and patients' response to immunosuppressive therapies.
Serological evidence of previous exposure to EBV in children with MS supports a role for EBV infection early in MS pathogenesis, as already indicated by prospective studies in adults. Higher antibody titers and T-cell responses to EBV in patients compared to healthy EBV carriers indicate possible continuous viral reactivation, whereas there is some evidence that EBV could break immune tolerance to myelin antigens through molecular mimicry. Detection of EBV-infected B-cells in patients' brain raises the possibility that intrathecal B-cell abnormalities and T-cell-mediated immunopathology in MS are the consequence of a persistently dysregulated EBV infection. Accordingly, targeting T-cells and/or B-cells with monoclonal antibody therapies ameliorates MS. Whether EBV has a causative or pathogenic role in MS can now be addressed in relation to genetic, hormonal and other environmental influences that may affect EBV-host interactions.
By shedding light on the involvement of EBV in MS, these findings will pave the way to disease prevention and increase the therapeutic index of future treatments.