The role of Epstein-Barr virus in the etiology of multiple sclerosis: a current review

ABSTRACT

Introduction: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. While its exact etiology is unknown, it is generally believed that MS is caused by environmental triggers in genetically predisposed individuals. Strong and consistent evidence suggests a key role of Epstein-Barr virus (EBV), a B lymphotropic human gammaherpesvirus, in the etiology of MS.

Areas covered: This review summarizes recent developments in the field of EBV and MS with a focus on potential mechanisms underlying the role of EBV in MS. PubMed was searched for the terms ‘Epstein-Barr virus’ and ‘multiple sclerosis’.

Expert opinion: The current evidence is compatible with the working hypothesis that MS is a rare complication of EBV infection. Under the premise of a causative role of EBV in MS, it needs to be postulated that EBV causes a specific, and likely persistent, change(s) that is necessarily required for the development of MS. However, although progress has been made, the nature of that change and thus the precise mechanism explaining the role of EBV in MS remain elusive. The mechanism of EBV in MS therefore is a pressing question, whose clarification may substantially advance the pathophysiological understanding, rational therapies, and prevention of MS.

KEYWORDS:

• Multiple sclerosis
• Epstein-Barr virus
• etiology
• risk factor
• antibodies
• seropositivity
• seroprevalence

Article highlights

• The evidence for an association of EBV and MS is based on a practically universal EBV seropositivity in patients with MS, an increased risk of MS following IM, elevated EBV antibody levels in presymptomatic and manifest MS as well as seroconversion from EBV seronegativity to EBV seropositivity before the clinical onset of MS.

• The (sero)epidemiological data are compatible with the working hypothesis that MS is a rare complication of EBV infection, meaning that EBV plays a causative role in MS.

• Under the premise of a causative role of EBV in MS, it must be postulated that EBV infection occasionally causes some specific change(s) that is necessary for development of MS.

• The precise mechanism through which EBV infection leads to the development of MS is currently unknown.

• The mechanism of EBV in MS appears to be a pressing question, whose elucidation would substantially advance the pathophysiological understanding as well as rational therapies and prevention of MS.

Declaration of interest

KR received research support from Novartis, Merck Serono, German Ministry of Education and Research, European Union (821,283-2), Stiftung Charité (BIH Clinical Fellow Program) and Arthur Arnstein Foundation; received speaker honoraria and travel grants from Bayer, Biogen Idec, Merck Serono, sanofi-aventis/Genzyme, Teva, Roche, Novartis, and Guthy Jackson Charitable Foundation. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This work was supported by Stiftung Charité (BIH Clinical Fellow Program), grant number: [BIH_PRO_551].