1887

Abstract

SUMMARY

The neurovirulence of eight temperature-sensitive () mutants of mouse hepatitis virus strain A59 in 4-week-old BALB/c mice was investigated. Whereas a dose of 100 p.f.u. of wild-type virus killed mice within a week, a 1000-fold higher dose of mutants did not. Three mutants induced demyelinating disease in the central nervous system (CNS). The pathology of the demyelinating disease caused by one mutant, designated 342, was studied in detail. Pathological changes, starting 3 days post-inoculation (p.i.), were characterized by inflammation and demyelination in the CNS. Antibody responses directed against all virus-specific structural proteins were present at 7 days p.i. No virus particles were observed by electron microscopy at 14 days p.i. However, macrophages and lymphocytes were abundant in the areas of demyelination. The growth kinetics of wild-type virus, -342 and a revertant of -342 were compared. Wild-type virus and the revertant replicated rapidly in the brain and spread to the liver causing a lethal hepatitis. -342, however, replicated to a much lesser extent within the brain and could not be detected in the blood or liver. The lesion in the genome of -342 seems, therefore, to determine the outcome of the infection.

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1987-03-01
2022-01-22
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