Viruses and Multiple Sclerosis: From Mechanisms and Pathways to Translational Research Opportunities

Abstract

Viruses are directly or indirectly implicated in multiple sclerosis (MS). Here, we review the evidence on the virus-related pathophysiology of MS, introduce common experimental models, and explore the ways in which viruses cause demyelination. By emphasizing knowledge gaps, we highlight future research directions for effective MS diagnostics and therapies: (i) identifying biomarkers for at-risk individuals, (ii) searching for direct evidence of specific causative viruses, (iii) establishing the contribution of host genetic factors and viruses, and (iv) investigating the contribution of immune regulation at extra-CNS sites. Research in these areas is likely to be facilitated by the application of high-throughput technologies, the development of systems-based bioinformatic approaches, careful selection of experimental models, and the acquisition of high-quality clinical material for tissue-based research.

Increased Serological Response Against Human Herpesvirus 6A Is Associated With Risk for Multiple Sclerosis

“…Similar interaction with HLA has previously been reported for immune response to EBV (19). How these interactions fit with the previously suggested mechanisms for how viruses can trigger autoimmunity, like molecular mimicry and bystander activation (55,56), as well as interactions with other viruses not studied here (57,58), remains to be determined and the present study adds to the complexity regarding the specificity explained by these mechanisms.…”

Microbiome in Multiple Sclerosis: Where Are We, What We Know and Do Not Know

“…However, the clinical relevance-with respect to whether these alterations contribute towards susceptibility for MS or, instead, they exert a relative protective effect-remains controversial both for adult [53,54] and pediatric populations [55,56]. In 2016, two case control studies reported distinct patterns of gut microbiota composition by the use of 16S ribosomal ribonucleic acid rRNA metagenomics analysis [57,58] (for further discussion on the potential of metagenomic techniques as applied to MS, see [59,60]). These studies provided evidence of reduced diversity in the gut microbiome of MS patients compared to controls.…”

“…MS is a complex autoimmune disease with clinical variability. As such, the establishment of a causative role for intestinal microbiota towards disease pathogenesis requires combined efforts from the field of metagenomics and other "-omics" approaches [59,60,111] with the capacity for high throughput data production and the application of these data in the context of translational medicine.…”

COVID-19 Immunopathology and the Central Nervous System: Implication for Multiple Sclerosis and Other Autoimmune Diseases with Associated Demyelination

“…The potential of SARS-CoV-2 for direct CNS invasion poses a special challenge for MS. Coronaviruses have been previously shown to invade the CNS (reviewed in [ 51 , 52 ]) and to induce direct neuron loss [ 34 ]. A similar potential for SARS-CoV-2 remains to be elucidated; however, if proven, it would suggest that COVID-19 in the context of MS further predisposes PwMS towards neurodegeneration, a pathological component also recognized early in the course of the disease.…”