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Infection, Interaction and the Expression of Virulence by Defined Strains of Semliki Forest Virus

Microbiological Research Establishment, Porton Down, Salisbury, Wiltshire, England

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.

Received 21 March 1972; accepted 9 May 1972.