Genetic control of resistance to street rabies virus in mice

Resistance to intraperitoneally inoculated street rabies virus (SRV) in mice was shown to be under genetic control. SJL/J, CBA/J, DBA/2J, and BALB/cAn mice were resistant, whereas A/WySn/J and A.SW/SnJ mice were susceptible. In addition, female mice of the resistant BALB/cAn and DBA/2J strains were more resistant than their male counterparts. Resistance was not controlled solely by the major histocompatibility locus because susceptible A.SW/SnJ and resistant SJL/J mice have the same H-2S haplotype. Challenge of F1 hybrids produced by crossing resistant and susceptible strains indicated resistance was dominant (97% survivors). Inoculation of backcross mice produced by mating F1 hybrids with susceptible parents showed that one and/or two genes controlled susceptibility. Furthermore, inoculation of SRV obtained from six different animals indicated that differences in strain susceptibilities were not dependent on the SRV isolate. Genetic control of resistance to SRV was, however, abrogated by intracerebral inoculation of virus. Resistant strains of mice were detected that either remained asymptomatic or, in contrast, developed signs of clinical disease, but disease failed to progress and they survived. The recognition of resistant and susceptible strains of mice, differences in female-male resistance within the same resistant strain, as well as dissimilar clinical responses in different resistant mouse strains to intraperitoneally inoculated SRV provide promising probes for investigation of host resistance and mechanisms for survival after onset of clinical rabies.