Multiple sclerosis affects nearly 2.9 million people globally, yet its root cause has resisted a clean explanation for decades. A growing body of evidence now places viral exposure — particularly by members of the herpesvirus family — at the center of MS pathogenesis, reshaping how researchers conceptualize the disease's earliest triggering events and potentially how it might one day be intercepted before symptoms emerge.
This comprehensive review, published in Virology Journal, synthesizes evidence implicating six specific viruses in MS development: Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), varicella-zoster virus, herpes simplex virus 1, cytomegalovirus, and SARS-CoV-2. Across these pathogens, the review identifies converging mechanisms — molecular mimicry, autoreactive T- and B-cell activation, and virus-driven neuroinflammation — through which exposure in genetically susceptible individuals may initiate immune-mediated demyelination. Critically, the authors argue that viral infection likely represents a permissive early event rather than a direct cause, priming downstream immune dysregulation that eventually crosses a pathological threshold. Latent infections with periodic reactivation are also proposed as a plausible driver of MS's characteristic relapsing-remitting pattern.
The EBV connection is the most robustly supported. A landmark 2022 military cohort study of over 10 million U.S. service members demonstrated a 32-fold increase in MS risk following EBV seroconversion, placing it closer to a necessary — though not sufficient — condition for disease. The inclusion of SARS-CoV-2 in this review is timely and reflects emerging post-pandemic data suggesting COVID-19 may represent a new environmental trigger in predisposed individuals, though evidence remains far less mature than for herpesviruses. From a translational standpoint, the therapeutic implications are substantial: EBV-targeting T-cell immunotherapy trials are already underway, and antiviral strategies could theoretically be incorporated into early MS risk management. The primary limitation here is that a narrative review synthesizes existing literature without new data, meaning mechanistic claims are dependent on the quality of underlying studies — many of which remain observational or preclinical. Still, this represents a valuable synthesis of a rapidly evolving field with genuine paradigm-shifting potential.