The Interaction between Viral and Environmental Risk Factors in the Pathogenesis of Multiple Sclerosis

Abstract

Multiple sclerosis (MS) is a chronic debilitating inflammatory disease of unknown ethology targeting the central nervous system (CNS). MS has a polysymptomatic onset and is usually first diagnosed between the ages of 20–40 years. The pathology of the disease is characterized by immune mediated demyelination in the CNS. Although there is no clinical finding unique to MS, characteristic symptoms include sensory symptoms visual and motor impairment. No definitive trigger for the development of MS has been identified but large-scale population studies have described several epidemiological risk factors for the disease. This list is a confusing one including latitude, vitamin D (vitD) levels, genetics, infection with Epstein Barr Virus (EBV) and endogenous retrovirus (ERV) reactivation. This review will look at the evidence for each of these and the potential links between these disparate risk factors and the known molecular disease pathogenesis to describe potential hypotheses for the triggering of MS pathology.

PD-1 and PD-L1 Expression on Circulating Lymphocytes as a Marker of Epstein-Barr Virus Reactivation-Associated Proliferative Glomerulonephritis

“…The life cycle of EBV is particularly complex and the virus undergoes the latency phase during which it expresses several genes impacting oncogenesis [44][45][46][47]. Recent studies have shown that EBV DNA is present in large quantities in patients with autoimmune diseases of several etiologies [48,49]. However, there are no proofs on the effect of EBV reactivation on the expression of PD-1 and PD-L1 antigens in patients with primary GN.…”

A practical view of fine-mapping and gene prioritization in the post-genome-wide association era

“…In six out of the seven autoimmune disorders tested, RELI identified that 130 out of 1953 candidate causal variants [12] overlapped with EBNA2 binding sites in B-cell lines identified by ChIP-seq [51]. Interestingly, many autoimmune diseases, including coeliac disease and multiple sclerosis [52,53], are thought to be partially triggered by viral infections, suggesting that variants may only be causal when viral factors are also present. Moreover, TF motifs can be highly degenerate, and a small change in TF binding affinity can induce a subtle dosage effect on the activity of a regulatory region [44].…”

Viral infections and multiple sclerosis

“…Some aspects of its etiology and pathogenesis are still unclear, however it is generally accepted that MS is an inflammatory disease with autoimmune characteristics influenced by environmental or infectious factors in genetically susceptible individuals. These factors are supposed to interplay to varying extent, contributing to the heterogeneity of MS [2].…”