Multiple sclerosis and infection: history, EBV, and the search for mechanism

SUMMARY Infection has long been hypothesized as the cause of multiple sclerosis (MS), and recent evidence for Epstein-Barr virus (EBV) as the trigger of MS is clear and compelling. This clarity contrasts with yet uncertain viral mechanisms and their relation to MS neuroinflammation and demyelination. As long as this disparity persists, it will invigorate virologists, molecular biologists, immunologists, and clinicians to ascertain how EBV potentiates MS onset, and possibly the disease’s chronic activity and progression. Such efforts should take advantage of the diverse body of basic and clinical research conducted over nearly two centuries since the first clinical descriptions of MS plaques. Defining the contribution of EBV to the complex and multifactorial pathology of MS will also require suitable experimental models and techniques. Such efforts will broaden our understanding of virus-driven neuroinflammation and specifically inform the development of EBV-targeted therapies for MS management and, ultimately, prevention.