Temperature-sensitive mutants of rabies virus in mice: a mutant (ts2) revertant mixture selectively pathogenic by the peripheral route of inoculation

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Abstract
Analysis of the pathogenic potential in mice of a variety of rabies and rabies serogroup viruses revealed that an apparently revertant population of virus derived from CVS mutant ts 2 had a unique capacity to selectively induce paralytic disease when given by a peripheral [intraplantar (i.pl.)] route of inoculation. Little paralytic disease was induced by high concentrations of virus administered by the intracerebral (i.c.) route; paralytic disease and death were characteristically induced in mice given only a few infectious doses of virus i.c. Disease induced by i.pl. inoculation was dose dependent. Mice frequently survived paralytic disease induced by i.pl. inoculation, with clinical signs often persisting indefinitely; mice surviving i.c. inoculation of high concentrations of virus frequently exhibited chronic nonspecific signs of minor debility. Analysis of the ts 2 virus population indicated that it was composed of a mixture of ts and revertant virions, each with characteristic pathogenic (or nonpathogenic) propensities, none of which was identical to the original composite ts 2 virus populations. Despite the heterogeneity of the ts 2 virus population, the typical pathogenic pattern of selective pathogenic capacity after i.pl. inoculation at high dosese was retained during 11 consecutive passages in suckling mouse brain. ts 2 Virus interfered with the disease producing capacity of CVS fixed rabies virus when ts 2-CVS mixtures were inoculated i.c. Attempts to demonstrate a particular propensity for induction in vitro of autointerference by ts 2 in serial passage in [baby hamster kidney] BHK-21 cell culture inoculated at high multiplicity were unsuccessful.