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. 1981 Oct;78(10):6446–6450. doi: 10.1073/pnas.78.10.6446

Episomal simian virus 40 genomes in human brain tumors.

P Krieg, E Amtmann, D Jonas, H Fischer, K Zang, G Sauer
PMCID: PMC349056  PMID: 6273871

Abstract

Eight out of 35 human intracranial tumors were shown by restriction enzyme analysis to contain unintegrated simian virus 40 (SV40) DNA molecules. The relative amount of viral DNA was estimated to be the equivalent of one viral genome within every 10th to 20th cell. No infectious virus was detected in tissue cultures established from the tumors. From only one tumor was it possible to rescue, by cell fusion, infectious SV40 displaying wild-type properties. In those cases that permitted a more detailed analysis, the restriction enzyme cleavage patterns appeared to correspond to the wild-type patterns with one exception, in which the SV40 episomes displayed a deletion of approximately 70 base pairs close to the origin of DNA replication. From one tumor, the SV40 genomes were transferred into permissive CV-1 monkey cells by transfection with the total tumor DNA. Despite their persistence as episomes no infectious virus was produced. Furthermore, no viral antigens were detectable, although the SV40 messengers for the small and the large tumor antigens were present. These cells had, however, acquired the ability to form colonies in low concentrations of serum. Thus this report provides, by restriction enzyme analysis, direct evidence for the presence of SV40 DNA in human tumors.

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Selected References

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

  1. Amtmann E., Müller H., Sauer G. Equine connective tissue tumors contain unintegrated bovine papilloma virus DNA. J Virol. 1980 Sep;35(3):962–964. doi: 10.1128/jvi.35.3.962-964.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Denhardt D. T. A membrane-filter technique for the detection of complementary DNA. Biochem Biophys Res Commun. 1966 Jun 13;23(5):641–646. doi: 10.1016/0006-291x(66)90447-5. [DOI] [PubMed] [Google Scholar]
  3. Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
  4. Gross-Bellard M., Oudet P., Chambon P. Isolation of high-molecular-weight DNA from mammalian cells. Eur J Biochem. 1973 Jul 2;36(1):32–38. doi: 10.1111/j.1432-1033.1973.tb02881.x. [DOI] [PubMed] [Google Scholar]
  5. Howley P. M., Khoury G., Takemoto K. K., Martin M. A. Polynucleotide sequences common to the genomes of simian virus 40 and the human papovaviruses JC and BK. Virology. 1976 Aug;73(1):303–307. doi: 10.1016/0042-6822(76)90084-2. [DOI] [PubMed] [Google Scholar]
  6. Khoury G., Howley P. M., Garon C., Mullarkey M. F., Takemoto K. K., Martin M. A. Homology and relationship between the genomes of papovaviruses, BK virus and simian virus 40. Proc Natl Acad Sci U S A. 1975 Jul;72(7):2563–2567. doi: 10.1073/pnas.72.7.2563. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Krieg P., Amtmann E., Sauer G., Lavi S., Kleinberger T., Winocour E. The integrated SV40 genome in permissive transformed monkey cells. Virology. 1981 Jan 30;108(2):453–461. doi: 10.1016/0042-6822(81)90452-9. [DOI] [PubMed] [Google Scholar]
  8. Law M. F., Lowy D. R., Dvoretzky I., Howley P. M. Mouse cells transformed by bovine papillomavirus contain only extrachromosomal viral DNA sequences. Proc Natl Acad Sci U S A. 1981 May;78(5):2727–2731. doi: 10.1073/pnas.78.5.2727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. London W. T., Houff S. A., Madden D. L., Fuccillo D. A., Gravell M., Wallen W. C., Palmer A. E., Sever J. L., Padgett B. L., Walker D. L. Brain tumors in owl monkeys inoculated with a human polyomavirus (JC virus). Science. 1978 Sep 29;201(4362):1246–1249. doi: 10.1126/science.211583. [DOI] [PubMed] [Google Scholar]
  10. MORRIS J. A., JOHNSON K. M., AULISIO C. G., CHANOCK R. M., KNIGHT V. Clinical and serologic responses in volunteers given vacuolating virus (SV-40) by respiratory route. Proc Soc Exp Biol Med. 1961 Oct;108:56–59. doi: 10.3181/00379727-108-26843. [DOI] [PubMed] [Google Scholar]
  11. Major E. O., Di Mayorca G. Malignant transformation of BHK21 clone 13 cells by BK virus--a human papovavirus. Proc Natl Acad Sci U S A. 1973 Nov;70(11):3210–3212. doi: 10.1073/pnas.70.11.3210. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Meinke W., Goldstein D. A., Smith R. A. Simian virus 40-related DNA sequences in a human brain tumor. Neurology. 1979 Dec;29(12):1590–1594. doi: 10.1212/wnl.29.12.1590. [DOI] [PubMed] [Google Scholar]
  13. Mullarkey M. F., Hruska J. F., Takemoto K. K. Comparison of two human papovaviruses with simian virus 40 by structural protein and antigenic analysis. J Virol. 1974 May;13(5):1014–1019. doi: 10.1128/jvi.13.5.1014-1019.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Padgett B. L., Walker D. L. New human papovaviruses. Prog Med Virol. 1976;22:1–35. [PubMed] [Google Scholar]
  15. Pontecorvo G. Production of mammalian somatic cell hybrids by means of polyethylene glycol treatment. Somatic Cell Genet. 1975 Oct;1(4):397–400. doi: 10.1007/BF01538671. [DOI] [PubMed] [Google Scholar]
  16. Portolani M., Barbanti-Brodano G., Placa M. L. Malignant transformation of hamster kidney cells by BK virus. J Virol. 1975 Feb;15(2):420–422. doi: 10.1128/jvi.15.2.420-422.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Scherneck S., Lübbe L., Geissler E., Nisch G., Rudolph M., Wählte H., Weickmann F., Zimmermann W. Detection of simian virus 40 related T-antigen in human meningiomas. Zentralbl Neurochir. 1979;40(2):121–130. [PubMed] [Google Scholar]
  18. Scherneck S., Rudolph M., Geissler E., Vogel F., Lübbe L., Wählte H., Nisch G., Weickmann F., Zimmermann W. Isolation of a SV40-like Papovavirus from a human glioblastoma. Int J Cancer. 1979 Nov 15;24(5):523–531. doi: 10.1002/ijc.2910240502. [DOI] [PubMed] [Google Scholar]
  19. Shah K. V., Daniel R. W., Strandberg J. D. Sarcoma in a hamster inoculated with BK virus, a human papovavirus. J Natl Cancer Inst. 1975 Apr;54(4):945–950. [PubMed] [Google Scholar]
  20. Shah K., Nathanson N. Human exposure to SV40: review and comment. Am J Epidemiol. 1976 Jan;103(1):1–12. doi: 10.1093/oxfordjournals.aje.a112197. [DOI] [PubMed] [Google Scholar]
  21. Sharp P. A., Pettersson U., Sambrook J. Viral DNA in transformed cells. I. A study of the sequences of adenovirus 2 DNA in a line of transformed rat cells using specific fragments of the viral genome. J Mol Biol. 1974 Jul 15;86(4):709–726. doi: 10.1016/0022-2836(74)90348-9. [DOI] [PubMed] [Google Scholar]
  22. Soriano F., Shelburne C. E., Gökcen M. Simian virus 40 in a human cancer. Nature. 1974 May 31;249(456):421–424. doi: 10.1038/249421a0. [DOI] [PubMed] [Google Scholar]
  23. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  24. Steffen M., Krieg P., Pernfuss M., Sauer E., Eisinger V., Sauer G. Growth dynamics of a latent primate papovavirus. J Virol. 1980 Sep;35(3):865–875. doi: 10.1128/jvi.35.3.865-875.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Takemoto K. K., Linke H., Miyamura T., Fareed G. C. Persistent BK papovavirus infection of transformed human fetal brain cells. I. Episomal viral DNA in cloned lines deficient in T-antigen expression. J Virol. 1979 Mar;29(3):1177–1185. doi: 10.1128/jvi.29.3.1177-1185.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Takemoto K. K., Martin M. A. Transformation of hamster kidney cells by BK papovavirus DNA. J Virol. 1975 Jan;17(1):247–253. doi: 10.1128/jvi.17.1.247-253.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Takemoto K. K., Rabson A. S., Mullarkey M. F., Blaese R. M., Garon C. F., Nelson D. Isolation of papovavirus from brain tumor and urine of a patient with Wiskott-Aldrich syndrome. J Natl Cancer Inst. 1974 Nov;53(5):1205–1207. doi: 10.1093/jnci/53.5.1205. [DOI] [PubMed] [Google Scholar]
  28. Tegtmeyer P., Macasaet F. Simian virus 40 deoxyribonucleic acid synthesis: analysis by gel electrophoresis. J Virol. 1972 Oct;10(4):599–604. doi: 10.1128/jvi.10.4.599-604.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Tegtmeyer P., Rundell K., Collins J. K. Modification of simian virus 40 protein A. J Virol. 1977 Feb;21(2):647–657. doi: 10.1128/jvi.21.2.647-657.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Weiss A. F., Portmann R., Fischer H., Simon J., Zang K. D. Simian virus 40-related antigens in three human meningiomas with defined chromosome loss. Proc Natl Acad Sci U S A. 1975 Feb;72(2):609–613. doi: 10.1073/pnas.72.2.609. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Yogo Y., Furuno A., Watanabe S., Yoshiike K. Occurrence of free, defective viral DNA in a hamster tumor induced by human papovavirus BK. Virology. 1980 May;103(1):241–244. doi: 10.1016/0042-6822(80)90143-9. [DOI] [PubMed] [Google Scholar]
  33. ter Schegget J., Voves J., van Strien A., van der Noordaa J. Free viral DNA in BK virus-induced hamster tumor cells. J Virol. 1980 Aug;35(2):331–339. doi: 10.1128/jvi.35.2.331-339.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]

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