Summary
Due to the varying length (12 to 30 hours) of the “latent period” (phase 1) in individual cells the onset of the production of polyoma virus (phase 2) in contact-inhibited mouse kidney cells is very asynchronous.
In polyoma-infected mouse tissue cultures cellular and viral DNA synthesis are inhibited efficiently by 5-fluorodeoxyuridine. If DNA synthesis is blocked, the transcription of “late” viral messenger RNA and the formation of capsid protein are inhibited. These inhibitory effects of 5-fluorodeoxyuridine are reversed by thymidine. The “early” events, however, of the infective cycle that lead to the activation of the cellular DNA-synthesizing apparatus take place in the presence of 5-fluorodeoxyuridine and hence do not depend on DNA replication. In the presence of the inhibitor the activated cells accumulate, ready to start DNA synthesis synchronously after the release of the inhibition by thymidine.
The conclusion is reached that in contact-inhibited mouse kidney cells infection with polyoma virus activates specifically the cellular DNA-synthesizing apparatus without triggering the entire mitotic machinery.
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References
Benjamin, T. L.: Virus-specific RNA in cells productively infected or transformed by polyoma virus. J. molec. Biol.16, 359–373 (1966).
Bresnick, E.: Early changes in pyrimidine biosynthesis after partial hepatectomy. J. biol. Chem.240, 2550–2556 (1965).
Cerottini, J.-C., andK. T. Brunner: Localization of mouse isoantigens on the cell surface as revealed by immunofluorescence. Immunology13, 395–403 (1967).
Cleaver, J. E., andR. M. Holford: Investigations into the incorporation of (3H) thymidine into DNA in L-strain cells and the formation of a pool of phosphorylated derivatives during pulse-labelling. Biochim. biophys. Acta (Amst.)103, 654–671 (1965).
Cohen, S. S., J. G. Flaks, H. D. Barner, M. R. Loeb, andJ. Lichtenstein: The mode of action of 5-fluorouracil and its derivatives. Proc. nat. Acad. Sci. (Wash.)44, 1004–1012 (1958).
Cooper, H. L., andA. D. Rubin: Synthesis of nonribosomal RNA by lymphocytes: A response to phytohemagglutinin treatment. Science152, 516–518 (1966).
Defendi, V., andF. Taguchi: Studies with the complement fixing antigen induced by polyoma virus. Ann. Med. exp. Fenn.44, 232–241 (1966).
Dulbecco, R., L. H. Hartwell, andM. Vogt: Induction of cellular DNA synthesis by polyoma virus. Proc. nat. Acad. Sci. (Wash.)53, 403–410 (1965).
Eagle, H.: Amino acid metabolism in mammalian cell cultures. Science130, 432–437 (1959).
Eddy, B. E., andS. E. Stewart: Physical properties, and hemagglutinating and cytopathogenic effects of the SE polyoma virus. In Proc. third Canad. Cancer Conf., p. 307–324. Academic Press, Inc., New York (1959).
Epstein, R. H., A. Bolle, C. M. Steinberg, E. Kellenberger, E. Boy de la Tour, R. Chevalley, R. S. Edgar, M. Susman, G. H. Denhardt, andA. Lielausis: Physiological studies of conditional lethal mutants of bacteriophage T4D. Cold Spr. Harb. Symp. quant. Biol.28, 375–392 (1963).
Flanagan, J. F., andH. S. Ginsberg: Synthesis of virus-specific polymers in adenovirus-infected cells: Effect of 5-fluorodeoxyuridine. J. exp. Med.116, 141–157 (1962).
Frearson, P. M., S. Kit, andD. R. Dubbs: Deoxythymidylate synthetase and deoxythymidine kinase activities of virus-infected animal cells. Cancer Res.25, 737–744 (1965).
Habel, K.: Virus tumor antigens: Specific fingerprints ? Cancer Res.26, 2018–2024 (1966).
Hartwell, L. H., M. Vogt, andR. Dulbecco: Induction of cellular DNA synthesis by polyoma virus: Increase in the rate of enzyme synthesis after infection with polyoma virus in mouse kidney cells. Virology27, 262–272 (1965).
Hirt, B.: Evidence for semiconservative replication of circular polyoma DNA. Proc. nat. Acad. Sci. (Wash.)55, 997–1004 (1966).
Hirt, B.: Selective extraction of polyoma DNA from infected mouse cell cultures. J. molec. Biol.26, 365–369 (1967).
Horowitz, J., andE. Chargaff: Massive incorporation of 5-fluorouracil into a bacterial ribonucleic acid. Nature (Lond.)184, 1213–1215 (1959).
Huxley, H. E., andG. Zubay: Preferential staining of nucleic acid-containing structures for electron microscopy. J. Biophys. biochem. Cytol.11, 273–296 (1961).
Jacob, F., andJ. Monod: Genetic regulatory mechanisms in the synthesis of proteins. J. molec. Biol.3, 318–356 (1961).
Kára, J., andR. Weil: Specific activation of the DNA-synthesizing apparatus in contact-inhibited mouse kidney cells by polyoma virus. Proc. nat. Acad. Sci. (Wash.)57, 63–70 (1967).
Karnovsky, M. J.: Simple methods for “staining with lead” at high pH in electron microscopy. J. Biophys. biochem. Cytol.11, 729–732 (1961).
Kit, S., andD. R. Dubbs: Properties of deoxythymidine kinase partially purified from noninfected and virus-infected mouse fibroblast cells. Virology26, 16–27 (1965).
Kit, S., D. R. Dubbs, andP. M. Frearson: Enzymes of nucleic acid metabolism in cells infected with polyoma virus. Cancer Res.26, 638–646 (1966).
Lieberman, I., R. Abrams, N. Hunt, andP. Ove: Levels of enzyme activity and deoxyribonucleic acid synthesis in mammalian cells cultured from the animal. J. biol. Chem.238, 3955–3962 (1963).
Lieberman, I., R. Abrams, andP. Ove: Changes in the metabolism of ribonucleic acid preceding the synthesis of deoxyribonucleic acid in mammalian cells cultured from the animal. J. biol. Chem.238, 2141–2149 (1963).
Lieberman, I., andP. Kane: Synthesis of ribosomes in the liver after partial hepatectomy. J. biol. Chem.240, 1737–1741 (1965).
Marinozzi, V., etA. Gautier: Essais de cytochimie ultrastructurale. Du rôle de l'osmium réduit dans les “colorations” électroniques. C. R. Acad. Sci. (Paris)253, 1180–1182 (1961).
Morishima, A., M. M. Grumbach, andJ. H. Taylor: Asynchronous duplication of human chromosomes and the origin of sex chromatin. Proc. nat. Acad. Sci. (Wash.)48, 756–763 (1962).
Ouchterlony, Ö.: Diffusion-in-gel methods for immunological analysis II. Progr. Allergy6, 30–154 (1962).
Parker, R. C.: Methods of tissue culture, p. 77. Hoeber, New York, 3rd ed. (1961).
Rapp, F., J. S. Butel, L. A. Feldman, T. Kitahara, andJ. L. Melnick: Differential effects of inhibitors on the steps leading to the formation of SV40 tumor and virus antigens. J. exp. Med.121, 935–944 (1965).
Rosenkranz, H. S.: A non-nucleotide polymer found in the DNA of the sand dollar,Echinarachnius parma. II. Preliminary characterization. Canad. J. Biochem.45, 281–287 (1967).
Schildkraut, C. L., J. Marmur, andP. Doty: Determination of the base composition of deoxyribonucleic acid from its buoyant density in CsCl. J. molec. Biol.4, 430–443 (1962).
Sheinin, R.: Studies on the effect of 5-fluoro-2′-deoxyuridine on polyoma T formation in mouse embryo cells. Virology22, 368–376 (1964).
Takemoto, K. K., R. A. Malmgren, andK. Habel: Immunofluorescent demonstration of polyoma tumor antigen in lytic infection of mouse embryo cells. Virology28, 485–488 (1966).
Vinograd, J., R. Bruner, R. Kent, andJ. Weigle: Band-centrifugation of macromolecules and viruses in self-generating density gradients. Proc. nat. Acad. Sci. (Wash.)49, 902–910 (1963).
Vinograd, J., andJ. E. Hearst: Equilibrium sedimentation of macromolecules and viruses in a density gradient. Progr. Chem. org. nat. Prod.20, 372–422 (1962).
Vogt, M., andR. Dulbecco: Steps in the neoplastic transformation of hamster embryo cells by polyoma virus. Proc. nat. Acad. Sci. (Wash.)49, 171–179 (1963).
Weil, R., M. R. Michel, andG. K. Ruschmann: Induction of cellular DNA synthesis by polyoma virus. Proc. nat. Acad. Sci. (Wash.)53, 1468–1475 (1965).
Weil, R., G. Pétursson, J. Kára, andH. Diggelmann: On the interaction of polyoma virus with the genetic apparatus of host cells. InJ. S. Colter (ed.). The Molecular Biology of Viruses. Academic Press, Inc., New York (1967).
Weil, R., andJ. Vinograd: The cyclic helix and cyclic coil forms of polyoma viral DNA. Proc. nat. Acad. Sci. (Wash.)50, 730–738 (1963).
Winocour, E.: Purification of polyoma virus. Virology19, 158–168 (1963).
Wood, B. T., S. H. Thompson, andG. Goldstein: Fluorescent antibody staining III. Preparation of fluorescein-isothiocyanate-labeled antibodies. J. Immunol.95, 225–229 (1965).
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Pétursson, G., Weil, R. A study on the mechanism of polyoma-induced activation of the cellular DNA-synthesizing apparatus. Archiv f Virusforschung 24, 1–29 (1968). https://doi.org/10.1007/BF01242898
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DOI: https://doi.org/10.1007/BF01242898