Epstein–Barr virus and multiple sclerosis: potential opportunities for immunotherapy

Abstract

Multiple sclerosis (MS) is a common chronic inflammatory demyelinating disease of the central nervous system (CNS) causing progressive disability. Many observations implicate Epstein–Barr virus (EBV) in the pathogenesis of MS, namely universal EBV seropositivity, high anti-EBV antibody levels, alterations in EBV-specific CD8+ T-cell immunity, increased spontaneous EBV-induced transformation of peripheral blood B cells, increased shedding of EBV from saliva and accumulation of EBV-infected B cells and plasma cells in the brain. Several mechanisms have been postulated to explain the role of EBV in the development of MS including cross-reactivity between EBV and CNS antigens, bystander damage to the CNS by EBV-specific CD8+ T cells, activation of innate immunity by EBV-encoded small RNA molecules in the CNS, expression of αB-crystallin in EBV-infected B cells leading to a CD4+ T-cell response against oligodendrocyte-derived αB-crystallin and EBV infection of autoreactive B cells, which produce pathogenic autoantibodies and provide costimulatory survival signals to autoreactive T cells in the CNS. The rapidly accumulating evidence for a pathogenic role of EBV in MS provides ground for optimism that it might be possible to prevent and cure MS by effectively controlling EBV infection through vaccination, antiviral drugs or treatment with EBV-specific cytotoxic CD8+ T cells. Adoptive immunotherapy with in vitro-expanded autologous EBV-specific CD8+ T cells directed against viral latent proteins was recently used to treat a patient with secondary progressive MS. Following the therapy, there was clinical improvement, decreased disease activity on magnetic resonance imaging and reduced intrathecal immunoglobulin production.

High-Density Peptide Microarray Analysis of IgG Autoantibody Reactivities in Serum and Cerebrospinal Fluid of Multiple Sclerosis Patients

“…The EBV-mediated transformation of infected B cells, which confers resistance to apoptosis, may pose a challenge. On the other hand, a dysregulated EBV-specific immune control in MS patients may contribute to autoimmune processes (86). A major antigen of EBV is EBNA1, a multifunctional DNA-binding protein maintaining the virus in latently infected proliferating cells (87).…”

Prevalence of Herpes Simplex Virus Infection in Patients With Relapsing-Remitting Multiple Sclerosis: A Case-Control Study in the North of Iran

“…According to the clinical presentation and the histopathological properties of MS lesions, a viral infection could be responsible for the MS development (3). Nowadays, high prevalence of herpesviruses such as Epstein-Barr and varicella-zoster, as well as herpes simplex virus (HSV) are found in acute MS patients, but absent in the healthy control groups (4)(5)(6).…”

Emerging Concepts on the Gut Microbiome and Multiple Sclerosis

“…Environmental associations with the risk of MS development are greatly varied; those confirmed include lower vitamin D levels, cigarette smoking, viral infection (Epstein-Barr virus), and obesity, although this list is suspected to be incomplete (Hedstrom and others 2012;Summerday and others 2012;Wingerchuk 2012;Pender and Burrows 2014). Since the incidence of MS has increased in many locations throughout the world, there is increased attention focused on identifying other environmental risk factors for MS.…”