PATHOGENESIS OF MOUSE HEPATITIS VIRUS-INDUCED DEMYELINATION

Infection of rodents with neurotropic mouse hepatitis virus (MHV) may result in lethal encephalitis or paralytic demyelinating disease resem bling the human disease multiple sclerosis. The outcome of MHV infecti on is dependent on a number of variables, including the passage histor y of the viral isolate, dose and route of inoculation, and the age and immune status of the host. Alterations in surface glycoproteins, espe cially the spike protein, can profoundly influence pathogenesis. Innat e resistance to MHV infection may be related to the expression of cell ular receptors or to immunological factors. The immune system plays a major role in MHV pathogenesis, affecting encephalitis, viral clearanc e, and demyelination. Antiviral antibodies, CD4(+) T lymphocytes, or C D8(+) T lymphocytes may protect infected animals from lethal encephali tis, but both CD4(+) and CD8(+) T lymphocytes are required for effecti ve viral clearance. Demyelination in MHV-infected animals has been att ributed to the cytolytic effects of viral infection on myelin-producin g oligodendrocytes, but more recent evidence supports an immunopatholo gical mechanism for demyelination. Immunopathological models far demye lination include autoimmunity, direct immune cytotoxicity, and indirec t 'bystander' damage. Although evidence exists supporting all of these models, the authors favor the bystander demyelination mo del. Much re mains to be revealed about the processes leading to demyelination in M HV-infected mice, and information gained from these investigations may aid in the study of demyelinating disease in humans.