title: Pathogenesis of mouse hepatitis virus-induced demyelination.
abstract: Infection of rodents with neurotropic mouse hepatitis virus (MHV) may result in lethal encephalitis or paralytic demyelinating disease resembling the human disease multiple sclerosis. The outcome of MHV infection is dependent on a number of variables, including the passage history of the viral isolate, dose and route of inoculation, and the age and immune status of the host. Alterations in surface glycoproteins, especially the spike protein, can profoundly influence pathogenesis. Innate resistance to MHV infection may be related to the expression of cellular receptors or to immunological factors. The immune system plays a major role in MHV pathogenesis, affecting encephalitis, viral clearance, and demyelination. Antiviral antibodies, CD4+ T lymphocytes, or CD8+ T lymphocytes may protect infected animals from lethal encephalitis, but both CD4+ and CD8+ T lymphocytes are required for effective viral clearance. Demyelination in MHV-infected animals has been attributed to the cytolytic effects of viral infection on myelin-producing oligodendrocytes, but more recent evidence supports an immunopathological mechanism for demyelination. Immunopathological models for demyelination include autoimmunity, direct immune cytotoxicity, and indirect 'bystander' damage. Although evidence exists supporting all of these models, the authors favor the bystander demyelination model. Much remains to be revealed about the processes leading to demyelination in MHV-infected mice, and information gained from these investigations may aid in the study of demyelinating disease in humans.
authors.affiliation: Department of Medical Microbiology, University of Wisconsin, Madison 53706, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Houtman
authors.forename: J O
authors.initials: JO
authors.lastname: Fleming
mesh_terms: D000818:Animals; D018352:Coronavirus Infections; D003711:Demyelinating Diseases / Q000821:virology*; D006801:Humans; D051379:Mice; D006517:Murine hepatitis virus / Q000472:pathogenicity*; D014774:Virulence