Virulence of polioviruses in relation to variant characteristics distinguishable on cells in vitro

Early terminal-dilution end point passages of the poliovirus strains Akron (antigenic type 1), Brooks (type 2), and Mabie (type 3) in monkey kidney tissue cultures resulted in the emergence of viruses of reduced virulence for monkeys. This reduction in virulence has not as yet been found to be associated with any change in the virus observable on cells in vitro. Through the use of specific selective environments, several variant viruses, which are characterizable on cells in vitro, were obtained from these viruses of reduced virulence. The distinguishing characteristics of these variant viruses are HeLa-adaptation, altered response to cystine, and cold-adaptation. Tests in monkeys showed that virulence is essentially independent of HeLa-adaptation and cystine-response. The cold-adapted viruses obtained by passage in monkey kidney tissue cultures at 30°, however, were found to be even less virulent than their only moderately virulent ancestors. Viruses further adapted to the cold were obtained by passage at 23° and were found not only to be more cold-adapted but also to be more avirulent than their progenitor 30°-adapted viruses. One of these 23°-adapted variants (Mabie) has shown no virulence for the monkey by the intraspinal route of inoculation. These cold adapted viruses are deadapted to monkey kidney tissue cultures at temperatures as high as 37° and the data indicate that the virulence of these viruses is negatively correlated with the degree of this deadaptation. The relative avirulence of a cold-adapted virus therefore appears to be due to its generally reduced capacity to propagate at 37° or above.