Theiler's virus infection: a model for multiple sclerosis.
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.
Oleszak
Emilia L
EL
Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, Pennsylvania 19106, USA. emelia.oleszak@temple.edu
Chang
J Robert
JR
Friedman
Herman
H
Katsetos
Christos D
CD
Platsoucas
Chris D
CD
D000818:Animals; D018188:Cardiovirus Infections / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D006801:Humans; D018448:Models, Immunological; D009103:Multiple Sclerosis / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D017945:Theilovirus / Q000472:pathogenicity*