Temperature-Sensitivity Characteristics Distinguishing Substrains of Fixed Rabies Virus: Lack of Correlation with Plaque-Size Markers or Virulence for Mice

Abstract

Three characteristics of a variety of strains and substrains of cell culture-adapted rabies virus were examined: (1) relative capacity to replicate at 40.5 C (rct/40.5 marker); (2) plaque size in agarose-suspended baby-hamster kidney cells (subclone 13S); and (3) relative pathogenicity for adult mice. Each of four strains of fixed virus was capable of replication at 40.5 C, but quantitative differences in rct/40.5 efficiency, which did not correlate with virulence for mice, were noted. In addition, two substrains of challenge-virus-standard (CVS) cultivated at 23 C25 C and three temperature-sensitive mutants, all incapable of replication at 40.5 C, retained normal virulence for mice. CVS variants tested in the course of continuous passage in snake or lizard cell cultures became incapable of replication at 40.5 C at different passage levels, a phenomenon not related temporally to the acquisition of attenuation for mice or small-plaque markers in the same substrains. The independent variation of these three phenotypic characters suggests that they are controlled by different segments of the viral genome.