Theiler's Virus Infection: a Model for Multiple Sclerosis

Abstract

Both genetic background and environmental factors, very probably viruses, appear to play a role in the etiology of multiple sclerosis (MS). Lessons from viral experimental models suggest that many different viruses may trigger inflammatory demyelinating diseases resembling MS. Theiler's virus, a picornavirus, induces in susceptible strains of mice early acute disease resembling encephalomyelitis followed by late chronic demyelinating disease, which is one of the best, if not the best, animal model for MS. During early acute disease the virus replicates in gray matter of the central nervous system but is eliminated to very low titers 2 weeks postinfection. Late chronic demyelinating disease becomes clinically apparent approximately 2 weeks later and is characterized by extensive demyelinating lesions and mononuclear cell infiltrates, progressive spinal cord atrophy, and axonal loss. Myelin damage is immunologically mediated, but it is not clear whether it is due to molecular mimicry or epitope spreading. Cytokines, nitric oxide/reactive nitrogen species, and costimulatory molecules are involved in the pathogenesis of both diseases. Close similarities between Theiler's virus-induced demyelinating disease in mice and MS in humans, include the following: major histocompatibility complex-dependent susceptibility; substantial similarities in neuropathology, including axonal damage and remyelination; and paucity of T-cell apoptosis in demyelinating disease. Both diseases are immunologically mediated. These common features emphasize the close similarities of Theiler's virus-induced demyelinating disease in mice and MS in humans

Is systemic sclerosis an antigen‐driven T cell disease?

“…Molecular mimicry is defined as the sharing of common epitopes between microorganisms (such as viruses) and host proteins (for review, see ref. 147). T cells that recognize viral determinants may recognize, by molecular mimicry, host determinants that are shared with the virus, even long after the virus is no longer present.…”

Circulation of 3 Lineages of a Novel Saffold Cardiovirus in Humans

“…TMEV comprises strains of differing neuropathogenicity, which constitute accepted mouse models of either human acute poliomyelitis or disseminated encephalomyelitis. The latter is indistinguishable from multiple sclerosis in humans (4,5).…”

“…Notably, most recently identifi ed viruses that show no overt disease association do not grow in culture (36)(37)(38). Second, the murine cardioviruses, and especially TMEV, the closest relative to SafV, display a range of clinical associations that are dependent on strain properties (4,(27)(28)(29)(30). The existence of high and low pathogenic variants most likely provides advantages in the interplay between host population density, herd immunity, and viral replicative fi tness.…”

“…Neurovirulent strains, such as GDVII, cause an acute encephalomyelitis in mice, resulting in a high proportion of deaths. Persistent strains like BeAn and DA cause a chronic demyelinating disease that provides an experimental animal model for multiple sclerosis in humans (4,(27)(28)(29)(30). These drastically different disease patterns seem to be determined by conformational changes in the outermost structures of VP1 and VP2 (31).…”

Etiology and Pathogenisis of Aortic Aneurysm

“…A small number of studies have concentrated on multiplex AAA families (with at least 2 affected members) (Platsoucas et al, 2006;Oleszak et al, 2004). Genome-wide scans of these patients have suggested a role for genes located on chromosome 19q13 and 4q31.47.…”