Genetic Control of Resistance to Street Rabies Virus

It is well known that not all animals manifesting clinical signs of street rabies virus (SRV) 1 infection die. These observations have been made in natural (1-4) and experimental infections (5-12). In one study, it was shown that 16% of outbred Swiss Webster mice inoculated intraperitoneally (i.p.) with SRV survived after developing signs of illness and that recovery was associated with high levels of rabies virusneutralizing antibody in the brain (5). In contrast, Baer and associates (12) have shown that little, if any, SRV-neutralizing antibody was present in brains of Swiss ICR mice that survived with sequelae of infection after peripheral inoculation of SRV. The importance of virus-neutralizing antibody in brains of mice in one model of sickness with recovery, but not the other, is perplexing. This difference might be explained by the genetic constitution of the host in that it has been shown that immunized substrains of outbred Swiss mice vary in their resistance to rabies virus (13, 14). Furthermore, greater vaccine protection has been obtained in Swiss than non-Swiss mice (15). To more adequately define parameters responsible for resistance/susceptibility to SRV infection, and for recovery from infection after onset of clinical signs, it is important to study a host in which all members behave identically. Thus, several t inbred mouse strains were tested in the anticipation that strains would be identified that responded differently to SRV. It is shown that there was a marked variation in strain susceptibility to i.p. inoculated SRV and that resistance was genetically controlled. Furthermore, clinical signs were apparent only occasionally in mice of some resistant strains. Mice of other resistant strains developed these signs, but disease failed to progress and they survived.