VARIATION IN VIRULENCE 233 



poliovirus has been shown to be influenced by the type of cell used for tissue 

 cultures as well as the constitution and pH of the medium (Li, 1957). These 

 studies, however, have so far not been conducted with pure clones of 

 virus; consequently, what is potentially an extremely interesting situation 

 has yet to be exploited. Similarly, it has been shown that cells which are 

 incapable of yielding virus when infected in the host will proceed to develop 

 virus if taken from the animal and grown in vitro (Kaplan, 1955). Thus, 

 environment may have a marked effect on the potentiality for cells to support 

 virus multiplication. 



Other variants with reduced neuropathogenicity have been demonstrated 

 to arise in tissue cultures. Such are the minute plaque variants of MEF-1 

 which appear in the presence of bovine serum (Takemori et al., 1957), and the 

 variants of several strains which are capable of multiplying in monkey 

 kidney cells at 30°C. (Dubes and Chapin, 1956). In the latter case, it is 

 tempting to believe that the lowered neuropathogenicity is a simple con- 

 sequence of a development of marked heat sensitivity; certainly it was only 

 in those cases where the mutant proved incapable of multiplying in monkey 

 kidney cells at 37°C. that neuropathogenicity was lowered. 



Where looked for, there has been ample evidence of inhomogeneity of 

 various lines of poliovirus. Heat-inactivation curves show the concavity 

 which would result from inhomogeneity; part of this is due to stable characters 

 which breed true on further passage (Stanley et al., 1956), and part is due to 

 some phenotypic difference not apparently reflected in genotype (Pohjanpelto, 

 1958). In this respect, poliovirus, in its heat-stability, is like certain bacterio- 

 phages (Adams, 1953) and viruses of the influenza group (Jones, 1945; 

 Goldman and Hanson, 1955). 



Just as poliovirus can be shown to vary in its host range, so can certain 

 lines of once-cloned cell lines be shown to contain subpopulations with 

 varying susceptibility to poliovirus which breed true (Vogt and Dulbecco, 

 1958). The more resistant types have a very low probability of being infected 

 on meeting a virus particle; hence, with such cells, it is possible to establish 

 infected cultures in which cell and virus multiplication can apparently 

 coexist indefinitely unless something disturbs the balance (Vogt and Dulbecco, 

 1958). Whether it would be possible to select for new virus types, capable of 

 infecting these resistant cells, has not yet been determined; this step has been 

 taken only in a rather more complex situation (Sabin, 1952). However, there 

 is every reason to believe that, as for bacteria and bacteriophages, both host 

 cell and virus enjoy variation in susceptibility and host-range, respectively. 

 The mechanism of cell insusceptibility in this case is probably not 

 dependent upon the absence of adsorption (Vogt and Dulbecco, 1958), 

 and so is not comparable to most examples of bacterial mutation to phage 

 resistance. 



