Neurotropic virus-host relationship alterations due to variation in viral genome as studied by electron microscopy

Abstract

A series of experiments has been described in which litters of suckling rats were inoculated either with wild-type reovirus type III or one of two of its temperature-sensitive (ts) mutants. While the wild-type virus produced an acute, fatal syndrome, the ts mutants were substantially less neurovirulent. Of the ts mutant-inoculated animals, a large percentage of the surviving (chronic) animals given ts mutant B showed an unobstructive hydrocephalus ex vacuo whereas chronic ts mutant C animals showed no visible nervous system disease. The ts mutants persisted within the central nervous system (CNS) for 6 to 8 weeks, after which they could not be detected either virologically, immunologically or morphologically. In another set of experiments, organized CNS explants were studied following infection with either measles virus or the neuroadapted Mantooth strain of SSPE virus, a variant of measles. Wild measles (Edmonston strain) exerted an acute destructive effect, but SSPE virus had a tendency to enter into coexistence with the tissue without destroying its organotypic nature. These relationships are somewhat reminiscent of the neuropathologic conditions caused by these two viruses in man. Since the reovirus type III ts mutants possess both genetic and morphologic defects and in many instances cause CNS conditions different from that induced by the wild-type virus, it has been proposed that a comparable situation may exist after measles and SSPE virus infection. SSPE virions of the strain studied were found to be defective in certain viral components which may have contributed to the lower neurovirulence and its entering into a chronic relationship with the CNS, in contrast to the acute destructive nature of measles infection. The findings are discussed in terms of relevance to other chronic CNS diseases, particularly multiple sclerosis, in which the possiblity exists that a mutant virus is operative.