246 F. FENNER AND J. CAIRNS 



occurring strains (whether highly virulent or not) multiplied to about the 

 same extent and at the same rate. However, the highly virulent strains 

 rapidly killed the host, whereas the common, moderately attenuated strains 

 produced many skin lesions which remained infective for mosquitoes for a 

 prolonged period. 



A field experiment in Australia, in 1954, demonstrated the high survival 

 advantage of the current strains (Femier et al., 1957). The highly virulent 

 European strain of virus was introduced on a large scale at the beginning of 

 the transmission season, in a rabbit population harboring the enzootic, 

 attenuated strain. Although the virulent European strain dominated the 

 peak of the epizootic, the local attenuated strain occurred in appreciable 

 numbers at the end of the epizootic and was the only type of virus to survive 

 through the ensuing winter. 



There is, of course, a delicate balance between the genetic resistance of 

 the host and the virulence of the virus. Tests on susceptible young wild 

 rabbits, obtained each spring over a period of five years from rabbit popula- 

 tions exposed annually to severe epizootics of myxomatosis, showed that there 

 had been a relatively rapid selection of genetically more resistant rabbits 

 (Marshall and Fenner, 1958). It is interesting to speculate upon the effect of 

 this change in host resistance on the selection of virus virulence: unless a 

 variant appears which multiplies predominantly in the skin, causing very 

 persistent virus-rich lesions, one might expect that more virulent strains 

 will be selected in the future, as they may cause in partially resistant hosts 

 the type of disease caused in susceptible hosts by the moderately attenuated 

 strains of virus. 



IV. Summary 



In this article we have traced the factors determining virulence for the host 

 from the simplest virus-host systems to the most complex and elaborate. 

 Wherever possible, we have chosen examples to demonstrate the effect of each 

 increase in order of complexity. But it is obvious that at the present time there 

 can be no over-all synthesis. The type of problem considered in simple 

 systems is quite different from that presented by complex systems, and it is 

 impossible to analyze the virulence of viruses for complex systems in terms 

 of those mechanisms demonstrated to operate in simple systems. This is 

 particularly unfortunate, as most of the work on variation in virulence of 

 animal viruses has, perforce, been conducted with the whole intact animal. 

 All that can be done is to discuss the different levels of complexity offered by 

 the various host systems which have been studied. We feel, however, that 

 only in such terms will it be possible ultimately to create a science of animal 

 virology. 



