Multiple sclerosis has long resisted a single explanatory framework, frustrating both patients and clinicians. A growing body of evidence now positions infectious exposures — not just genetic predisposition — as decisive forces that either ignite or suppress the autoimmune cascade underlying MS. This reframing carries real implications: if infections can both cause and potentially mitigate MS, therapeutic strategies might one day borrow tools from parasitology as much as from virology.
This review in Biomolecules synthesizes current evidence on how specific pathogens interact with MS pathophysiology through distinct immunological pathways. Epstein-Barr virus emerges as the most compelling viral candidate, operating primarily through antibody-mediated molecular mimicry — where EBV-generated antibodies cross-react with myelin antigens — and through dysregulation of B-cell populations that are already central targets of approved MS therapies. The review contrasts this pro-inflammatory viral axis with the paradoxically protective profile of parasitic organisms, particularly helminths and select protozoa, which appear to shift immune responses toward regulatory and tolerogenic phenotypes, dampening the neuroinflammation that drives demyelination and progressive neurodegeneration.
The juxtaposition of these two infectious categories is analytically valuable, though it also reveals the field's inherent complexity. The EBV-MS link has strengthened considerably since a landmark 2022 U.S. military cohort study demonstrated near-obligate EBV seropositivity preceding MS onset, lending biological plausibility to molecular mimicry mechanisms. The helminth hypothesis, by contrast, remains largely at the preclinical and observational level; clinical trials of deliberate helminth inoculation in MS patients have produced mixed results, suggesting that the immunomodulatory benefits seen in epidemiological data don't translate straightforwardly into therapeutic protocols. As a narrative review rather than a meta-analysis, this work synthesizes rather than adjudicates the evidence. Its primary value lies in framing infectious immunology as a legitimate therapeutic frontier for MS — potentially pointing toward microbiome modulation, anti-EBV vaccines, or refined B-cell targeting as the next generation of disease-modifying strategies.