How to and should we target EBV in MS?

ABSTRACT

Introduction

The etiology of multiple sclerosis (MS) remains unknown. Pathogenesis likely relies on a complex interaction between multiple environmental, genetic, and behavioral risk factors. However, a growing body of literature supports the role of a preceding Epstein-Barr virus (EBV) infection in the majority of cases.

Areas covered

In this narrative review, we summarize the latest findings regarding the potential role of EBV as a predisposing event inducing new onset of MS. EBV interactions with the genetic background and other infectious agents such as human endogenous retrovirus are explored. Additional data regarding the role of EBV regarding the rate of mid- and long-term disease progression is also discussed. Lastly, the effect of currently approved disease-modifying therapies (DMT) for MS treatment on the EBV-based molecular mechanisms and the development of new EBV-specific therapies are further reviewed.

Expert Opinion

Recent strong epidemiological findings support that EBV may be the primary inducing event in certain individuals that shortly thereafter develop MS. More studies are needed in order to better understand the significant variability in susceptibility based on environmental factors such as EBV exposure. Future investigations should focus on determining the specific EBV-related risk antigen(s) and phenotyping people with likely EBV-induced MS. Targeting EBV via several different avenues, including development of an EBV vaccine, may become the mainstay of MS treatment in the future.

KEYWORDS:

• EBV
• Epstein-Barr virus
• multiple sclerosis
• susceptibility
• disease progression
• EBV treatment
• anti-viral medications in MS
• EBV vaccine

Article highlights

• Increasing evidence suggests that Epstein-Barr Virus (EBV) may play a crucial role in the induction of multiple sclerosis (MS).

• The complex genetic and EBV interaction remains elusive, with only a small percentage of EBV-infected people developing MS.

• Therapies targeting EBV pathophysiological mechanisms and therapies with anti-viral effect have variable success and inconclusive outcomes.

• Novel vaccine development techniques could potentially improve their efficacy outcomes and be initially tested in high-risk, first-degree relatives of people with MS.

Declaration of interests

S Eckert has received compensation for speaking engagements from EMD Serono and has served on an advisory board for Genentech. D Jakimovski received personal compensation from EMD Serono and AstraZeneca for consultant fees. He received financial support for research activities from ClinSTAR by the National Institute of Aging (NIA) under award U24AG065204 and the Consortium of Multiple Sclerosis Centers (CMSC). He serves as the Associated Editor of Clinical Neurology and Neurosurgery and is compensated by Elsevier. R Zivadinov received personal compensation from Bristol Myers Squibb, Biogen Idec, EMD Serono, Sanofi, Mapi Pharma, Filterlex, 3D Communications for speaking and consultant fees. He received financial support for research activities from Bristol Myers Squibb, Novartis, CorEvitas, Mapi Pharma, Octave, EMD Serono and Protembis. M Hicar serves as a site primary investigator for Lyme vaccine and COVID therapy studies with Pfizer. He works as a consultant for the NIH and for the Erie County Department of Health and provides independent consulting on immunology and vaccine development. None of these projects overlap with content within this manuscript. B Weinstock-Guttman served as a consultant for Biogen, EMD Serono, Novartis, Genentech, Celgene/Bristol Meyers Squibb, Sanofi Genzyme, Bayer, Janssen, Sana, Labcorp and Horizon. She served in speaker bureau for Biogen. B Weinstock-Guttman also has received grant/research support from the agencies listed in the previous sentence. She serves in the editorial board for BMJ Neurology, Children, CNS Drugs, MS International and Frontiers Epidemiology.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.