230 F. FENNER AND J. CAIRNS 



vaccinia virus (Fenner and Comben, 1958). In both cases characters concerned 

 with pathogenicity or virulence behaved in a complex manner (as would be 

 expected from their nature) and cannot yet be analyzed physiologically or 

 genetically. However, genetic recombination should eventually prove a 

 powerful weapon for the analysis of these most obscure and complex aspects 

 of viral behavior. 



III. Animal Virus-Host Cell Systems 



It was noted earlier that all known associations of viruses with animals are 

 much more complex than the relation between a bacterial virus and its host. 

 For analytical purposes, however, it is possible to construct simpler artificial 

 systems or to utilize situations which do not involve the whole complex 

 activity of the animal. We shall consider three types of virus-cell system — 

 simple cell systems, analogous to the bacterial virus-bacterium system; struc- 

 turally complex but relatively self-contained cell systems, such as the chorio- 

 allantoic membrane of the chick embryo; and cell systems involving sequential 

 infection of a variety of organs. As a special case of the latter we shall 

 introduce sequential infection of individual animals, i.e., we shall extend our 

 study to include some epidemiological facets of adaptation and virulence. 



A. Simple Cell Systems 



This group comprises those examples of infection of cells by viruses in 

 which spread of infection from cell to cell is not limited by the nature of the 

 system and merely demands that, after infection of a cell, the progeny virus 

 is liberated from that cell in a form which can infect further cells. In this group 

 fall all examples of infection of cells in fluid suspension and also those examples 

 of infection of cells in sheets, where extension of infection from cell to cell can 

 occur freely by way of the overlying fluid. As examples of adaptation and 

 variation in such systems we will discuss the work done on the changes in 

 influenza virus on adaptation to the embryonated egg (the O-D change), and 

 on the variants of polio virus in tissue culture. In neither of these cases is the 

 problem of spread from cell to cell a deciding issue in the success of virus 

 multiplication. 



1 . The O-D Change of Influenza Virus 



This example of variation of an animal virus was the first to receive 

 detailed attention from the point of view both of the nature of the character 

 undergoing change and the manner in which the change occurred. On first 

 isolation, influenza A strains were found to agglutinate human and guinea 

 pig red cells more readily than fowl red cells (Burnet, 1942). On further 



