Epstein-Barr virus in multiple sclerosis

Abstract

Genetic and environmental factors determine the susceptibility to develop multiple sclerosis (MS). Improved epidemiologic study designs helped identify environmental risk associations for MS, such as a history of infectious mononucleosis (IM), a symptomatic primary infection with the human γ-herpesvirus Epstein-Barr virus (EBV). EBV preferentially infects B lymphocytes and persists lifelong in a transcriptionally quiescent state in circulating latently infected memory B cells (0.5 to 50 per million). Lytic EBV infection can occur from the memory B-cell pool, presumably after an encounter with the cognate B-cell receptor antigen. The immune control of EBV infection centers around strong memory CD4+ and CD8+ T-cell responses, whereby the CD4+ T cells maintain EBV-specific immunity, and both CD4+ and CD8+ T cells can target EBV-infected cells directly. Patients with MS are nearly universally seropositive for EBV (i.e., close to 100% in adults and >90% in children) compared with seropositivity rates of 90%–95% in adults and less than 80% in age-matched pediatric cohorts and show deregulated T-cell and antibody responses to EBV-encoded antigens. These changes are initiated early in disease development, since increased EBV-specific antibody titers are detectable as early as 5 or more years before the clinical onset of MS.1 In patients with clinically isolated syndromes and …