Neuropathogenicity of a mutant of mouse hepatitis virus, JHM strain, derived from persistently infected DBT cells.

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Subacute or chronic neuropathogenicity of a mutant mouse hepatitis virus (MHV), JHMcc, derived from DBT cell cultures persistently infected with MHV-JHM was studied in 4-week-old ICR mice. After intracerebral inoculation with 105 PFU of the virus, 80% of mice survived for 4 weeks, whereas the original MHV-JHM killed in a few days all mice inoculated with the same dose. The JHMcc titer of the brain reached a peak 4 or 5 days after infection and was still 103 PFU/0.2 g 10 days postinoculation. The virus-specific antigen was detected in neurons of the cerebral cortex and the medulla oblongata 4 weeks postinoculation. At an early stage of infection, moderate inflammation was produced in the cerebral cortex, whereas severe demyelination became distinct after degenerative and necrotic changes had subsided. Most of the mice surviving for 4 weeks postinoculation showed extensive demyelination and remyelination. These findings suggest that persistent infection of MHV-JHMcc in vivo may be established and that inflammatogenic effect and demyelination may be caused by different clones of MHV-JHM.