244 F. FENNER AND J. CAIRNS 



transmission is dependent upon the virus produced at the final sites of 

 multiplication (the skin and mucous membranes). Whether a virus is able to 

 invade the nervous system is, possibly with the exception of rabies virus and a 

 few others, immaterial to its survival: the ready multiplication of many 

 viruses, when implanted directly into the brain, contrasts sharply with the 

 rare occurrence of natural infection of the central nervous system. 



The next section illustrates the effect of this further restriction on the 

 selection of variants of different virulence, i.e., the necessity for efficient 

 transmission between different host animals. 



4. Myxomatosis 



Infectious myxomatosis, in laboratory rabbits, is another generalized 

 infection involving a sequential invasion of skin, lymph nodes, and vascular 

 endothelial cells, and culminating in a widespread secondary rash (Fenner and 

 Woodroofe, 1953). 



Myxoma virus originated in South America, where it is enzootic in the local 

 wild rabbit {Sylvilagus braziliensis). In this host it usually produces only a 

 single localized skin tumor, and is transmitted mechanically by mosquitoes 

 (Aragao, 1943). However, minute doses of myxoma virus, if transferred 

 directly from the skin lesion of a Sylvilagus rabbit to the skin of an Oryctolagus 

 rabbit, cause a very severe generalized disease, which is almost invariably 

 lethal. 



The deliberate introduction of myxomatosis into populations of wild 

 Oryctolagus rabbits in Australia in 1950 (Ratcliffe et al., 1952) and in Europe 

 in 1952 (Radot and Lepine, 1953) provided an opportunity to see what 

 changes in virulence would occur when a lethal generalized infection was 

 introduced into virgin populations. In the present context it allows us to 

 introduce a further factor into the sequence of events we have been discussing, 

 and one of major importance in natural infections, namely, transmission from 

 one animal in a population to another. Thus we may compare the simplest 

 situation in animal viruses (transfer from one individual cell to another 

 through a fluid menstruum) with one of the most complex (transfer from one 

 mammal to another by an intermediate vector, with a complex sequence of 

 events necessarily occurring in each mammalian host before the virus is 

 available for transfer to another mammal). 



With myxomatosis it is possible to use either the mortality rate or survival 

 time after infection as a direct measure of virulence (Fenner and Marshall, 

 1957). The reverse procedure, namely, challenge of rabbits from areas with 

 different histories of exposure to myxomatosis with one known strain of 

 virus, made it possible to observe changes in the genetic resistance of wild 

 rabbit populations (Marshall and Fenner, 1958). 



