234 F. FENNER AND J. CAIRNS 



3. Various Examples of Coexistence of Virus and Cell 



At various times, instances of the coexistence of virus and cell multiplica- 

 tion have been demonstrated. These are of relevance here in that they 

 represent a distinct type of interrelation of virus and cell which could be taken 

 to epitomize one type of avirulence. 



Production of vaccinia virus in roller tube cultures of fibroblasts was 

 suggested to occur without preventing continued multiplication of the 

 infected cells (Feller et al., 1940). The peaceful existence in Drosophila of the 

 virus of C0 2 -sensitivity and its transmission through the egg is another 

 example (L'Heritier, 1958), as must be all those cases where there is trans- 

 ovarial transmission in arthropods of viruses pathogenic for some other host 

 (Fukushi, 1933; Syverton and Berry, 1941; Florio and Stewart, 1947; Black, 

 1950). Indeed, it has yet to be shown that the multiplication of any of the 

 arthropod-borne viruses in their vectors is associated with any cell 

 destruction. 



None of these cases was amenable to the detailed quantitative investigation 

 which is necessary in order to prove that liberation of virus by the cell is not 

 necessarily associated with cell death. The establishmeDt of a carrier state in 

 tissue culture for poliovirus and NDV has recently been demonstrated 

 (Ackermann, 1957; Cieciura et al., 1957) and in these cases it should be 

 possible to demonstrate nonlethal virus liberation, if it happens. So far, only 

 for the infection of chicken fibroblasts by Rous sarcoma virus has it been 

 demonstrated that a cell may liberate virus and then give rise to a relatively 

 permanent line of multiplying cells, each of which liberates more virus 

 (Temin, 1958). 



These examples, some clear-cut, some merely suggestive, demonstrate the 

 difficulties inherent in any definition of virulence. Rous sarcoma virus 

 achieves its virulence for chickens by way of a relation with its host cell that 

 represents an extreme variety of avirulent infection. 



B. Structurally Complex Systevns 



In none of the examples of virus infection mentioned so far has there been 

 the need to consider the manner of spread of virus infection from cell to cell. 

 This great simplification was justified either because the example concerned 

 only the immediate effects of infection (i.e., the first cycle of multiplication) 

 or because the example concerned a host system in which it was reasonable to 

 assume that there was no limitation in the spread of infection from cell to 

 cell. However, when we consider that animals are characteristically multicel- 

 lular organisms, whose component cells are organized in highly ordered groups 

 often preserved behind a succession of defensive ramparts, it becomes 

 obvious that animal viruses must possess well-ordered powers of infection if 

 they are to spread successfully among the cells of their hosts. 



