Viruses and Multiple Sclerosis

Abstract

Multiple sclerosis (MS) is a chronic demyelinating disorder of unknown etiology, possibly caused by a virus or virus-triggered immunopathology. The virus might reactivate after years of latency and lyse oligodendrocytes, as in progressive multifocal leukoencephalopathy, or initiate immunopathological demyelination, as in animals infected with Theiler’s murine encephalomyelitis virus or coronaviruses. The argument for a viral cause of MS is supported by epidemiological analyses and studies of MS in identical twins, indicating that disease is acquired. However, the most important evidence is the presence of bands of oligoclonal IgG (OCBs) in MS brain and CSF that persist throughout the lifetime of the patient. OCBs are found almost exclusively in infectious CNS disorders, and antigenic targets of OCBs represent the agent that causes disease. Here, the authors review past attempts to identify an infectious agent in MS brain cells and discuss the promise of using recombinant antibodies generated from clonally expanded plasma cells in brain and CSF to identify disease-relevant antigens. They show how this strategy has been used successfully to analyze antigen specificity in subacute sclerosing panencephalitis, a chronic encephalitis caused by measles virus, and in neuromyelitis optica, a chronic autoimmune demyelinating disease produced by antibodies directed against the aquaporin-4 water channel.

Genomic analysis of ERVWE2 locus in patients with multiple sclerosis: absence of genetic association but potential role of human endogenous retrovirus type W elements in molecular mimicry with myelin antigen

“…Increased antibody titers were detected for Epstein-Barr, Varicella-Zoster, and Rubella Viruses, whereas specific proteins of human endogenous retrovirus (HERV), particularly from HERV-W family were evidenced in blood cells and brain lesions of MS patients (Antony et al, 2004a; Mameli et al, 2007; Owens et al, 2011; Perron et al, 2012). Also, EBV and HERV-W-associated superantigens where already hypothesized to contribute to MS pathogeny (Tai et al, 2008; Antony et al, 2011).…”

Intrathecal Humoral Immunity to Encephalitic RNA Viruses

“…The nervous system is a target for acute viral infections, as well as a reservoir of latent and persisting viruses [1,2,3,4,5,6,7]. In general, the absence of overt neurological deficits or pathology indicates effective immune control of persisting viruses in immunocompetent individuals.…”

“…Lastly, the CSF of MS patients harbors Ab to multiple viruses prevalent in the Western population, e.g. varicella zoster, rubella, HSV-1 and JC viruses [2,13]. These Ab appear to be markers of MS and are not indicative of active disease due to virus infection [2].…”

“…varicella zoster, rubella, HSV-1 and JC viruses [2,13]. These Ab appear to be markers of MS and are not indicative of active disease due to virus infection [2]. Nevertheless, the potential danger of losing control of persisting CNS viruses became apparent by the development of PML following rituximab (anti-CD20 monoclonal Ab) reduction of circulating B cells during therapy for rheumatoid arthritis [22] and MS [23].…”

Epstein-Barr virus is a necessary causative agent in the pathogenesis of multiple sclerosis: Commentary

“…1 It is thus with some scepticism that I view the significance of reports of the high prevalence of Epstein Barr antibodies in patients with multiple sclerosis. Even the significance of the finding that, when an sera are stored at an earlier date, those individuals who eventually developed multiple sclerosis had higher Epstein Barr serum titres in their stored serum than those who did not subsequently develop MS, is questionable; there is a long asymptomatic phase in MS, possibly extending up to 5 years or longer prior to clinical onset.…”