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Selective Killing of Simian Virus 40-transformed Human Fibroblasts by Parvovirus H-1¹

Laboratory of Biophysics and Radiobiology, Université Libre de Bruxelles, B-1640 Rhode St. Genèse, Belgium [Y. Q. C., F. d. F., J. H., B. L. A., J. J. C., J. R.], and Laboratory of Molecular Oncology, INSERM U186, Institut Pasteur de Lille, F-59019 Lille, France [B. L. A., J. J. C., J. R.]

A normal strain of human foreskin fibroblasts, two SV40-transformed derivatives with finite and infinite life spans, and an established line of SV40-transformed newborn human kidney cells are compared for their susceptibility to infection with parvovirus H-1. H-1 inocula, which do not detectably alter the growth of normal cells, cause a progressive degeneration of all three SV40-transformed cultures. The resistance of normal cells is not a membrane phenomenon since they adsorb and take up H-1 as efficiently as the transformants. Moreover, the fraction of infected cells supporting the synthesis and nuclear migration of H-1 proteins is similar in normal and SV40-transformed cultures. On the other hand, the enhanced H-1 sensitivity of transformed cells correlates with a 5- to 30-fold increase in their accumulation of newly synthesized parvoviral DNA, as compared with normal cultures. This stimulation of H-1 DNA replication is most pronounced for the amplification of duplex replicative forms, although the conversion of parental single-stranded DNA to replicative forms is also enhanced to a smaller extent. In addition, SV40-transformed cells support productive H-1 infection and release a burst of infectious virus, whereas no H-1 production can be detected in the normal cell strain. The latter difference was confirmed for another series of 7 normal and 16 SV40-transformed strains of human skin fibroblasts. Altogether, these results indicate that intracellular limitations on H-1 DNA replication are associated with the abortive nature of the parvoviral life cycle in normal human fibroblasts and are overcome after SV40 transformation, resulting in the selective killing of the transformants. This observation raises the possibility that oncolysis might contribute to the oncosuppressive activity displayed by parvoviruses in vivo.

¹ Supported by an Action de Recherche Concertée from the Ministère de la Politique Scientifique and by grants from the Caisse Générale d'Epargne et de Retraite, Loterie Nationale, and Fonds de la Recherche Scientifique Médicale.

² To whom requests for reprints should be addressed.

Received 11/12/85. Revised 3/ 5/86. Accepted 3/26/86.

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