MUTABILITY TOWARDS L PLAQUE CHARACTER OF ECHO VIRUS 19 S PARTICLES .I. VARIATION OF MUTATION RATE VALUES VERSUS MULTIPLICATION IN VARIOUS HOST CELL-MEDIUM SYSTEMS

The experimental conditions suitable for S→L mutation rate determination in ECHO virus 19 were investigated. Selection curves of L mutants during multicycle growth and S→L mutation rate determinations in single cycle growth of clonal S virus populations were performed on monkey kidney cultures with and without human embryo extract and, respectively, calf serum added as well as on human embryo cultures. The mutation rate values obtained varied for the same S clone with the selective effect of the host cell-medium system used even in single cycle growth experiments. On human embryo cultures (selectively favouring L particles) mutation-rate values were the highest, while on monkey kidney cells in the presence of human embryo extracts (with stabilizing effect on S virus) these values were lowest. Finally on unsupplemented monkey kidney cultures intermediate mutation rate values were recorded. It thus seems impossible to establish the exact role of mutation and that of favouring or limiting effects of selection in the S→L shift of ECHO virus 19 populations during in vitro passages. These findings also suggest that actual S→L mutation rate values could be obtained only on host cell systems selectively neutral" for parental S and mutant L particles. The impossibility to resolve this vicious cycle -i.e. necessity to know the rate of a mutational event prior to its determination - imposes specification of the host cell medium system in studies in which mutation rate determinations are performed. © 1968 Springer-Verlag."