GENETIC CHANGES IN ATTENUATED POLIOVIRUS STRAINS CULTIVATED ON HUMAN INTENSIVE IN VITRO1

Abstract
Human embryonic intestine in organ culture was found to support the multiplication of polioviruses for periods up to 4 months. The character of attenuated Type 3 strains following cultivation in this system was found to change from rct/40− to rct/40+, while Type 1 attenuated viruses remained rct/40− even after prolonged multiplication (up to 73 days in the same system). The growth rate of virulent H-24 strain was much higher than that of attenuated WM-3 virus in the intestinal explants. Similarly, an rct/40+ guanidine-re-sistant mutant of WM-3 virus, both singly and when mixed with the original rct/40− guanidine-sensitive strain, was more infectious and multiplied to higher riters in the explants. These results appear to be similar to the observed behavior of Type 3 virus strains in the human intestinal tract, and offer an explanation for the tendency to lose markers associated with attenuation.