Association of Multiple Sclerosis with Epstein-Barr virus Infection

Abstract

Purpose of Review: There is still controversy whether EBV could be a causative agent as opposed to an innocent bystander in the pathogenesis of multiple sclerosis (MS). We aimed to review main studies which were investigated the subject to reveal whether the presence of a possible latent or active infection with Epstein-Barr Virus (EBV) of people with MS could actually play a role in the development of the disease. This review summarizes current knowledge on the association of EBV and MS. Summary and Results: Multiple sclerosis (MS) is a demyelinating condition affecting the central nervous system. The etiology and pathogenesis of MS are unknown, but environmental agents and genetic susceptibility are likely to be involved. From the very early days of MS discovery, infections have been proposed to be the underlying causes of disease initiation. This assumption led to the development of the first FDA-approved immune-modulatory treatment for MS, Interferon-beta (IFN-b), known with its antiviral activities. It has been pointed out that a link between delayed infection with EBV and the development of MS is compatible with many unusual epidemiological features of the disease EBV infects more than 90% of all humans, most of whom remain healthy. In contrast, 99% of MS patients have evidence of prior infection with EBV. EBV infects resting B-lymphocytes, immortalizing them into long-lived memory B-cells that survive largely undetected by the immune system in the peripheral circulation. MS patients show elevated titers to EBV years before developing any neurologic symptoms. Postmortem pathologic analysis of brains of patients with MS has revealed diffuse EBV-associated B-cell dysregulation in all forms of MS. Theories of pathogenesis of EBV in MS include antigenic mimicry, immortalization of B-cell clones, and cytotoxic T-cell dysfunction against virally infected B cells. This article reviews the existing evidence of the relationship between EBV and MS.