Skip to main content
Journal of Virology logoLink to Journal of Virology
. 1989 Nov;63(11):4797–4807. doi: 10.1128/jvi.63.11.4797-4807.1989

Partial reversion of conditional transformation correlates with a decrease in the sensitivity of rat cells to killing by the parvovirus minute virus of mice but not in their capacity for virus production: effect of a temperature-sensitive v-src oncogene.

N Salome 1, B van Hille 1, M Geuskens 1, J Rommelaere 1
PMCID: PMC251117  PMID: 2507792

Abstract

The cytolytic effect of the autonomous parvovirus minute virus of mice, prototype strain (MVMp), was studied in cultures of ts 339/NRK rat cells that display a temperature-sensitive transformed phenotype as a result of their transformation with a Rous sarcoma virus strain matured in the v-src oncogene. A shift from restrictive (39.5 degrees C) to permissive (34.5 degrees C) temperature was associated with a marked sensitization of these cells to killing by MVMp. In contrast, ts 339/NRK cell derivatives supertransformed with a wild-type src oncogene were sensitive to MVMp at both temperatures, suggesting that the expression of a functional oncogene product may determine, at least in part, the extent of the parvoviral cytopathic effect. Although ts 339/NRK cells were quite resistant to parvoviral attack at 39.5 degrees C, they were similarly proficient in MVMp uptake, viral DNA and protein synthesis, and infectious particle production at both permissive and restrictive temperatures. Consistently, electron microscopic examination of infected ts 339/NRK cultures incubated at 39.5 degrees C revealed the presence, in the majority of the cells, of numerous full and empty virions that were predominantly located in autophagic-type vacuoles. Thus, in this system, the reversion of transformed and MVMp-sensitive phenotypes appears to correlate with the setting up of a noncytocidal mode of parvovirus production. These results raise the possibility that the physiological state of host cells may affect their susceptibility to parvoviruses by modulating not only their capacity for virus replication but also cellular processes controlling the cytopathic effect of viral products.

Full text

PDF

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson M. J., Pattison J. R. The human parvovirus. Brief review. Arch Virol. 1984;82(3-4):137–148. doi: 10.1007/BF01311158. [DOI] [PubMed] [Google Scholar]
  2. Berns K. I., Bohenzky R. A. Adeno-associated viruses: an update. Adv Virus Res. 1987;32:243–306. doi: 10.1016/s0065-3527(08)60479-0. [DOI] [PubMed] [Google Scholar]
  3. Chen Y. Q., de Foresta F., Hertoghs J., Avalosse B. L., Cornelis J. J., Rommelaere J. Selective killing of simian virus 40-transformed human fibroblasts by parvovirus H-1. Cancer Res. 1986 Jul;46(7):3574–3579. [PubMed] [Google Scholar]
  4. Clayson E. T., Brando L. V., Compans R. W. Release of simian virus 40 virions from epithelial cells is polarized and occurs without cell lysis. J Virol. 1989 May;63(5):2278–2288. doi: 10.1128/jvi.63.5.2278-2288.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Collett M. S., Purchio A. F., Erikson R. L. Avian sarcoma virus-transforming protein, pp60src shows protein kinase activity specific for tyrosine. Nature. 1980 May 15;285(5761):167–169. doi: 10.1038/285167a0. [DOI] [PubMed] [Google Scholar]
  6. Cooper J. A., Hunter T. Regulation of cell growth and transformation by tyrosine-specific protein kinases: the search for important cellular substrate proteins. Curr Top Microbiol Immunol. 1983;107:125–161. doi: 10.1007/978-3-642-69075-4_4. [DOI] [PubMed] [Google Scholar]
  7. Cornelis J. J., Becquart P., Duponchel N., Salomé N., Avalosse B. L., Namba M., Rommelaere J. Transformation of human fibroblasts by ionizing radiation, a chemical carcinogen, or simian virus 40 correlates with an increase in susceptibility to the autonomous parvoviruses H-1 virus and minute virus of mice. J Virol. 1988 May;62(5):1679–1686. doi: 10.1128/jvi.62.5.1679-1686.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cornelis J. J., Spruyt N., Spegelaere P., Guetta E., Darawshi T., Cotmore S. F., Tal J., Rommelaere J. Sensitization of transformed rat fibroblasts to killing by parvovirus minute virus of mice correlates with an increase in viral gene expression. J Virol. 1988 Sep;62(9):3438–3444. doi: 10.1128/jvi.62.9.3438-3444.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cotmore S. F., Tattersall P. The autonomously replicating parvoviruses of vertebrates. Adv Virus Res. 1987;33:91–174. doi: 10.1016/s0065-3527(08)60317-6. [DOI] [PubMed] [Google Scholar]
  10. Foulkes J. G., Erikson E., Erikson R. L. Separation of multiple phosphotyrosyl-and phosphoseryl-protein phosphatases from chicken brain. J Biol Chem. 1983 Jan 10;258(1):431–438. [PubMed] [Google Scholar]
  11. Garber E. A., Hanafusa T., Hanafusa H. Membrane association of the transforming protein of avian sarcoma virus UR2 and mutants temperature sensitive for cellular transformation and protein kinase activity. J Virol. 1985 Dec;56(3):790–797. doi: 10.1128/jvi.56.3.790-797.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Graf T., Friis R. R. Differential expression of transformation in rat and chicken cells infected with an avian sarcoma virus ts mutant. Virology. 1973 Nov;56(1):369–374. doi: 10.1016/0042-6822(73)90314-0. [DOI] [PubMed] [Google Scholar]
  13. Guetta E., Ron D., Tal J. Development-dependent replication of minute virus of mice in differentiated mouse testicular cell lines. J Gen Virol. 1986 Nov;67(Pt 11):2549–2554. doi: 10.1099/0022-1317-67-11-2549. [DOI] [PubMed] [Google Scholar]
  14. Huu Duc-Nguyen, Rosenblum E. N., Zeigel R. F. Persistent infection of a rat kidney cell line with Rauscher murine leukemia virus. J Bacteriol. 1966 Oct;92(4):1133–1140. doi: 10.1128/jb.92.4.1133-1140.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Jove R., Hanafusa H. Cell transformation by the viral src oncogene. Annu Rev Cell Biol. 1987;3:31–56. doi: 10.1146/annurev.cb.03.110187.000335. [DOI] [PubMed] [Google Scholar]
  16. Levinson A. D., Oppermann H., Varmus H. E., Bishop J. M. The purified product of the transforming gene of avian sarcoma virus phosphorylates tyrosine. J Biol Chem. 1980 Dec 25;255(24):11973–11980. [PubMed] [Google Scholar]
  17. Martin P., Henry C., Ferre F., Duterque-Coquillaud M., Lagrou C., Ghysdael J., Debuire B., Stehelin D., Saule S. Transformation of quail embryo fibroblasts by a retrovirus carrying a normal human c-myc gene. EMBO J. 1986 Jul;5(7):1529–1533. doi: 10.1002/j.1460-2075.1986.tb04393.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Merchlinsky M. J., Tattersall P. J., Leary J. J., Cotmore S. F., Gardiner E. M., Ward D. C. Construction of an infectious molecular clone of the autonomous parvovirus minute virus of mice. J Virol. 1983 Jul;47(1):227–232. doi: 10.1128/jvi.47.1.227-232.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Miller R. A., Ward D. C., Ruddle F. H. Embryonal carcinoma cells (and their somatic cell hybrids) are resistant to infection by the murine parvovirus MVM, which does infect other teratocarcinoma-derived cell lines. J Cell Physiol. 1977 Jun;91(3):393–401. doi: 10.1002/jcp.1040910309. [DOI] [PubMed] [Google Scholar]
  20. Mousset S., Cornelis J., Spruyt N., Rommelaere J. Transformation of established murine fibroblasts with an activated cellular Harvey-ras oncogene or the polyoma virus middle T gene increases cell permissiveness to parvovirus minute-virus-of-mice. Biochimie. 1986 Jul-Aug;68(7-8):951–955. doi: 10.1016/s0300-9084(86)81058-6. [DOI] [PubMed] [Google Scholar]
  21. Mousset S., Rommelaere J. Minute virus of mice inhibits cell transformation by simian virus 40. Nature. 1982 Dec 9;300(5892):537–539. doi: 10.1038/300537a0. [DOI] [PubMed] [Google Scholar]
  22. Mousset S., Rommelaere J. Susceptibility to parvovirus Minute virus of mice as a function of the degree of host cell transformation: little effect of simian virus 40 infection and phorbol ester treatment. Virus Res. 1988 Feb;9(2-3):107–117. doi: 10.1016/0168-1702(88)90026-3. [DOI] [PubMed] [Google Scholar]
  23. Nicolson G. L. Tumor cell instability, diversification, and progression to the metastatic phenotype: from oncogene to oncofetal expression. Cancer Res. 1987 Mar 15;47(6):1473–1487. [PubMed] [Google Scholar]
  24. Ozawa K., Ayub J., Kajigaya S., Shimada T., Young N. The gene encoding the nonstructural protein of B19 (human) parvovirus may be lethal in transfected cells. J Virol. 1988 Aug;62(8):2884–2889. doi: 10.1128/jvi.62.8.2884-2889.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Piwnica-Worms H., Saunders K. B., Roberts T. M., Smith A. E., Cheng S. H. Tyrosine phosphorylation regulates the biochemical and biological properties of pp60c-src. Cell. 1987 Apr 10;49(1):75–82. doi: 10.1016/0092-8674(87)90757-4. [DOI] [PubMed] [Google Scholar]
  26. Resh M. D., Erikson R. L. Highly specific antibody to Rous sarcoma virus src gene product recognizes a novel population of pp60v-src and pp60c-src molecules. J Cell Biol. 1985 Feb;100(2):409–417. doi: 10.1083/jcb.100.2.409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Rhode S. L., 3rd Construction of a genetic switch for inducible trans-activation of gene expression in eucaryotic cells. J Virol. 1987 May;61(5):1448–1456. doi: 10.1128/jvi.61.5.1448-1456.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Rhode S. L., 3rd Replication process of the parvovirus H-1 V. Isolation and characterization of temperature-sensitive H-1 mutants. J Virol. 1976 Feb;17(2):659–667. doi: 10.1128/jvi.17.2.659-667.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Richards R., Linser P., Armentrout R. W. Kinetics of assembly of a parvovirus, minute virus of mice, in synchronized rat brain cells. J Virol. 1977 Jun;22(3):778–793. doi: 10.1128/jvi.22.3.778-793.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Rigby P. W., Dieckmann M., Rhodes C., Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. doi: 10.1016/0022-2836(77)90052-3. [DOI] [PubMed] [Google Scholar]
  31. Rommelaere J., Vos J. M., Cornelis J. J., Ward D. C. UV-enhanced reactivation of minute-virus-of-mice: stimulation of a late step in the viral life cycle. Photochem Photobiol. 1981 Jun;33(6):845–854. doi: 10.1111/j.1751-1097.1981.tb05502.x. [DOI] [PubMed] [Google Scholar]
  32. Sefton B. M., Hunter T., Beemon K., Eckhart W. Evidence that the phosphorylation of tyrosine is essential for cellular transformation by Rous sarcoma virus. Cell. 1980 Jul;20(3):807–816. doi: 10.1016/0092-8674(80)90327-x. [DOI] [PubMed] [Google Scholar]
  33. Spalholz B. A., Tattersall P. Interaction of minute virus of mice with differentiated cells: strain-dependent target cell specificity is mediated by intracellular factors. J Virol. 1983 Jun;46(3):937–943. doi: 10.1128/jvi.46.3.937-943.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Tattersall P., Bratton J. Reciprocal productive and restrictive virus-cell interactions of immunosuppressive and prototype strains of minute virus of mice. J Virol. 1983 Jun;46(3):944–955. doi: 10.1128/jvi.46.3.944-955.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Tattersall P., Cawte P. J., Shatkin A. J., Ward D. C. Three structural polypeptides coded for by minite virus of mice, a parvovirus. J Virol. 1976 Oct;20(1):273–289. doi: 10.1128/jvi.20.1.273-289.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Toolan H. W., Rhode S. L., 3rd, Gierthy J. F. Inhibition of 7,12-dimethylbenz(a)anthracene-induced tumors in Syrian hamsters by prior infection with H-1 parvovirus. Cancer Res. 1982 Jul;42(7):2552–2555. [PubMed] [Google Scholar]
  37. Toolan H., Ledinko N. Growth and cytopathogenicity of H-viruses in human and simian cell cultures. Nature. 1965 Nov 20;208(5012):812–813. doi: 10.1038/208812a0. [DOI] [PubMed] [Google Scholar]
  38. Tullis G. E., Labieniec-Pintel L., Clemens K. E., Pintel D. Generation and characterization of a temperature-sensitive mutation in the NS-1 gene of the autonomous parvovirus minute virus of mice. J Virol. 1988 Aug;62(8):2736–2744. doi: 10.1128/jvi.62.8.2736-2744.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Van Hille B., Duponchel N., Salomé N., Spruyt N., Cotmore S. F., Tattersall P., Cornelis J. J., Rommelaere J. Limitations to the expression of parvoviral nonstructural proteins may determine the extent of sensitization of EJ-ras-transformed rat cells to minute virus of mice. Virology. 1989 Jul;171(1):89–97. doi: 10.1016/0042-6822(89)90514-x. [DOI] [PubMed] [Google Scholar]
  40. Vennström B., Kahn P., Adkins B., Enrietto P., Hayman M. J., Graf T., Luciw P. Transformation of mammalian fibroblasts and macrophages in vitro by a murine retrovirus encoding an avian v-myc oncogene. EMBO J. 1984 Dec 20;3(13):3223–3229. doi: 10.1002/j.1460-2075.1984.tb02282.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Welham M. J., Wyke J. A. A single point mutation has pleiotropic effects on pp60v-src function. J Virol. 1988 Jun;62(6):1898–1906. doi: 10.1128/jvi.62.6.1898-1906.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Winocour E., Keshet I. Indiscriminate recombination in simian virus 40-infected monkey cells. Proc Natl Acad Sci U S A. 1980 Aug;77(8):4861–4865. doi: 10.1073/pnas.77.8.4861. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Wolter S., Richards R., Armentrout R. W. Cell cycle-dependent replication of the DNA of minute virus of mice, a parvovirus. Biochim Biophys Acta. 1980 May 30;607(3):420–431. doi: 10.1016/0005-2787(80)90152-5. [DOI] [PubMed] [Google Scholar]
  44. Wyke J. A., Stoker A. W. Genetic analysis of the form and function of the viral src oncogene product. Biochim Biophys Acta. 1987 Apr 20;907(1):47–69. doi: 10.1016/0304-419x(87)90018-7. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES