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. 1982 Apr;79(8):2465–2469. doi: 10.1073/pnas.79.8.2465

Leukemogenesis by bovine leukemia virus: proviral DNA integration and lack of RNA expression of viral long terminal repeat and 3' proximate cellular sequences.

R Kettmann, J Deschamps, Y Cleuter, D Couez, A Burny, G Marbaix
PMCID: PMC346219  PMID: 6283527

Abstract

The DNA from 17 lymphoid tumors induced by bovine leukemia virus (BLV) was digested with the restriction endonuclease EcoRI. Filter hybridization analysis using radioactive probes specific for the BLV genome showed that all tumors contained at least one or a portion of one provirus. Digestion of these proviruses with Sac I demonstrated that deletions occurred in about 25% of the cases and involved sequences located in the 5' half of the provirus. No sequence homology was observed between the cloned proximate cellular sequences flanking two different proviruses at their 3' end and the corresponding sequences in 16 other tumor DNAs, thus showing that a wide range of genomic sites could accommodate BLV proviruses. Transcription of viral DNA including long terminal repeated sequences was not detected, strongly suggesting that viral gene expression is not required for maintenance of the tumor state. No expression of 3'-proximate cellular sequences was observed, indicating that no proximate downstream promotion took place in the cases examined.

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Selected References

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  1. Deschamps J., Kettmann R., Burny A. Experiments with cloned complete tumor-derived bovine leukemia virus information prove that the virus is totally exogenous to its target animal species. J Virol. 1981 Nov;40(2):605–609. doi: 10.1128/jvi.40.2.605-609.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Fung Y. K., Fadly A. M., Crittenden L. B., Kung H. J. On the mechanism of retrovirus-induced avian lymphoid leukosis: deletion and integration of the proviruses. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3418–3422. doi: 10.1073/pnas.78.6.3418. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Ghysdael J., Kettmann R., Burny A. Translation of bovine leukemia virus virion RNAs in heterologous protein-synthesizing systems. J Virol. 1979 Mar;29(3):1087–1098. doi: 10.1128/jvi.29.3.1087-1098.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Hare W. C., Yang T. J., McFeely R. A. A survey of chromosome findings in 47 cases of bovine lymphosarcoma (leukemia). J Natl Cancer Inst. 1967 Mar;38(3):383–392. [PubMed] [Google Scholar]
  5. Hayward W. S., Neel B. G., Astrin S. M. Activation of a cellular onc gene by promoter insertion in ALV-induced lymphoid leukosis. Nature. 1981 Apr 9;290(5806):475–480. doi: 10.1038/290475a0. [DOI] [PubMed] [Google Scholar]
  6. Kettmann R., Cleuter Y., Mammerickx M., Meunier-Rotival M., Bernardi G., Burny A., Chantrenne H. Genomic integration of bovine leukemia provirus: comparison of persistent lymphocytosis with lymph node tumor form of enzootic. Proc Natl Acad Sci U S A. 1980 May;77(5):2577–2581. doi: 10.1073/pnas.77.5.2577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Kettmann R., Couez D., Burny A. Restriction endonuclease mapping of linear unintegrated proviral DNA of bovine leukemia virus. J Virol. 1981 Apr;38(1):27–33. doi: 10.1128/jvi.38.1.27-33.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kettmann R., Marbaix G., Cleuter Y., Portetelle D., Mammerickx M., Burny A. Genomic integration of bovine leukemia provirus and lack of viral RNA expression in the target cells of cattle with different responses to BLV infection. Leuk Res. 1980;4(6):509–519. doi: 10.1016/0145-2126(80)90062-4. [DOI] [PubMed] [Google Scholar]
  9. Kettmann R., Portetelle D., Mammerickx M., Cleuter Y., Dekegel D., Galoux M., Ghysdael J., Burny A., Chantrenne H. Bovine leukemia virus: an exogenous RNA oncogenic virus. Proc Natl Acad Sci U S A. 1976 Apr;73(4):1014–1018. doi: 10.1073/pnas.73.4.1014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Maniatis T., Hardison R. C., Lacy E., Lauer J., O'Connell C., Quon D., Sim G. K., Efstratiadis A. The isolation of structural genes from libraries of eucaryotic DNA. Cell. 1978 Oct;15(2):687–701. doi: 10.1016/0092-8674(78)90036-3. [DOI] [PubMed] [Google Scholar]
  11. Neel B. G., Hayward W. S., Robinson H. L., Fang J., Astrin S. M. Avian leukosis virus-induced tumors have common proviral integration sites and synthesize discrete new RNAs: oncogenesis by promoter insertion. Cell. 1981 Feb;23(2):323–334. doi: 10.1016/0092-8674(81)90128-8. [DOI] [PubMed] [Google Scholar]
  12. Payne G. S., Courtneidge S. A., Crittenden L. B., Fadly A. M., Bishop J. M., Varmus H. E. Analysis of avian leukosis virus DNA and RNA in bursal tumours: viral gene expression is not required for maintenance of the tumor state. Cell. 1981 Feb;23(2):311–322. doi: 10.1016/0092-8674(81)90127-6. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Roussel M., Saule S., Lagrou C., Rommens C., Beug H., Graf T., Stehelin D. Three new types of viral oncogene of cellular origin specific for haematopoietic cell transformation. Nature. 1979 Oct 11;281(5731):452–455. doi: 10.1038/281452a0. [DOI] [PubMed] [Google Scholar]
  15. Shields A., Goff S., Paskind M., Otto G., Baltimore D. Structure of the Abelson murine leukemia virus genome. Cell. 1979 Dec;18(4):955–962. doi: 10.1016/0092-8674(79)90208-3. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. de Wet J. R., Daniels D. L., Schroeder J. L., Williams B. G., Denniston-Thompson K., Moore D. D., Blattner F. R. Restriction maps for twenty-one Charon vector phages. J Virol. 1980 Jan;33(1):401–410. doi: 10.1128/jvi.33.1.401-410.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]

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