Epstein-Barr virus and multiple sclerosis: from associations to mechanisms to potential therapies.

Abstract

Epstein-Barr virus, a widespread herpesvirus that establishes lifelong latency after primary infection, has emerged in serological and epidemiological studies as a strong and consistent risk factor for multiple sclerosis. Emerging evidence indicates that Epstein-Barr virus can interact with several multiple sclerosis susceptibility loci to modify the transcriptional programmes and differentiation trajectories of B cells. Specifically, Epstein-Barr virus infection has been associated with the expansion of neuroinvasive, atypical B cells, which are enriched in inflamed CNS compartments in people with multiple sclerosis and exhibit a strong capacity to stimulate autoreactive T cells. Dysregulation of Epstein-Barr virus latency by B cells, together with subtle deficiencies in T-cell-mediated control of Epstein-Barr virus, might further amplify the effect of these B cell-T cell interactions and predispose individuals to multiple sclerosis. WHERE NEXT?: These insights support the development of hypothesis-driven therapeutic strategies aimed at attenuating hyperactive autoimmune responses induced by Epstein-Barr virus and the autoimmune responses' access to the CNS. Strategies under investigation include prophylactic and therapeutic vaccines; allogeneic cytotoxic T lymphocytes specific for Epstein-Barr virus and designed to eliminate virus-infected cells; antibody-based and chimeric antigen receptor T-cell-based therapies targeting B-cell subsets induced by Epstein-Barr virus and migrate into the CNS; and conventional antiviral treatments. Together, these approaches might open new perspectives for both prevention and treatment of multiple sclerosis. Furthermore, they might help to clarify whether Epstein-Barr virus infection influences not only susceptibility to multiple sclerosis, but also disease activity and disability accrual after disease onset.