Pathogenicity for suckling mice of Coxsackie viruses adapted to human amnion cells.

Continuous passages in primary human amnion cell cultures of Coxsackie prototype viruses A-9, A-10, A-11, A-13, A-14, A-15, A-18, B-1, B-2, B-4, and B-5 increased the titers, hastened and enhanced cytopathic effect, and in varying degrees caused loss of virulence for newborn mice. Only B-3 behaved differently in that neither adaptation to cells in vitro nor attenuation with respect to the original animal host could be observed. Types A-15, B-1, B-2, and B-5 slowly regained virulence when passed in mice after high concentration passages in amnion cells whereas all other viruses reverted to their original virulence after only 1 or 2 passages in the animal host. When these strains, however, were purified by cloning procedures, they too showed markedly increased stability. In all stages of attenuation, viruses multiplied extensively in vivo as could be shown by titration in amnion cell cultures. It is suggested that a genetic mechanism is operative leading to virus populations in which the majority of the particles is qualitatively changed.