Abstract
In these studies in mice, guinea pigs and rabbits infected by intraperitoneal, intracerebral or respiratory routes, the expression of virulence by a virulent/avirulent mixture of known proportion depended on the administered dose and was not a simple marker for the virus population, or for the heterogeneous wild strain which it simulated. This dependence of the virulence of a virus sample upon its dose and heterogeneity is presented quantitatively for each host by a dose-response diagram which is the necessary extension of the simple dose-response curve. The latter may be used to express single response characteristics (death only, protection only) but is inappropriate to the expression of the present dual response-dose characteristics in which protection at low dose gives place to death at high dose, or vice versa. At some proportions of virulent/avirulent sub-populations in the virus inoculum even more complex dual response-dose characteristics may be generated. Thus the specification of virulence requires the presentation of a dose-response diagram for each relevant host and route of administration of virus.
Notwithstanding these seeming complications, basic types of virulent/avirulent interaction have been demonstrated and arranged in sequence according to the susceptibility or responsiveness of the host-route systems investigated. With closer definition of population heterogeneity and dose-response relationships, other virus-host-route systems will probably fit within similar sequences.
These results are interpreted in terms of a dynamic interaction between distinct lethal and protective responses and are relevant to problems involved in the design and testing of live vaccines.