Skip to main content
The EMBO Journal logoLink to The EMBO Journal
. 1983;2(6):805–809. doi: 10.1002/j.1460-2075.1983.tb01506.x

Two different types of transcription for the myelocytomatosis viruses MH2 and CMII.

S Saule, J Coll, M Righi, C Lagrou, M B Raes, D Stehelin
PMCID: PMC555193  PMID: 6315417

Abstract

The four avian defective leukemia retroviruses (DLVs) MC29, CMII, MH2 and OK10 all transform primarily macrophages in an in vitro bone marrow transformation assay, and contain specific nucleotide sequences closely related to the myc gene of MC29. These viruses were thought to express their oncogenic potential through a gag-myc fusion polyprotein, since fusion polyproteins were found in all tested cells transformed by MC29. We show here that MH2 virus does not conform to this model. Whereas MC29 produces only one mRNA detectable by RNA blotting in productively transformed cells, we reported recently that OK10 induced the synthesis of two myc-containing mRNAs, the smaller species being a spliced mRNA and a possible candidate for a transforming protein lacking gag determinants. However, the studies with OK10 were ambiguous because this virus produced also, in infected cells, a fusion protein containing gag, pol and myc determinants. We have therefore investigated the transcription pattern of the two other members of this group of viruses, namely CMII and MH2. Our results show that CMII resembles MC29 whereas MH2 produces, as OK10, two mRNAs containing myc-related sequences. However, unlike OK10, the MH2 fusion protein of 100 kd described previously cannot contain myc determinants and thus is likely to produce from its subgenomic mRNA a v-myc protein-lacking gag determinants. We thus conclude that the product of the v-myc oncogene is transforming with (MC29) or without (MH2) its fusion to gag determinants and that the multiple oncogenic spectrum is not basically affected since MH2 and MC29 both transform macrophages, fibroblasts and epithelial cells.

Full text

PDF
805

Images in this article

Selected References

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

  1. Abrams H. D., Rohrschneider L. R., Eisenman R. N. Nuclear location of the putative transforming protein of avian myelocytomatosis virus. Cell. 1982 Jun;29(2):427–439. doi: 10.1016/0092-8674(82)90159-3. [DOI] [PubMed] [Google Scholar]
  2. Alexander R. W., Moscovici C., Vogt P. K. Avian oncovirus Mill Hill No. 2: pathogenicity in chickens. J Natl Cancer Inst. 1979 Feb;62(2):359–366. [PubMed] [Google Scholar]
  3. Alwine J. C., Kemp D. J., Stark G. R. Method for detection of specific RNAs in agarose gels by transfer to diazobenzyloxymethyl-paper and hybridization with DNA probes. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5350–5354. doi: 10.1073/pnas.74.12.5350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bishop J. M., Courtneidge S. A., Levinson A. D., Oppermann H., Quintrell N., Sheiness D. K., Weiss S. R., Varmus H. E. Origin and function of avian retrovirus transforming genes. Cold Spring Harb Symp Quant Biol. 1980;44(Pt 2):919–930. doi: 10.1101/sqb.1980.044.01.099. [DOI] [PubMed] [Google Scholar]
  5. Bister K., Duesberg P. H. Genetic structure of avian acute leukemia viruses. Cold Spring Harb Symp Quant Biol. 1980;44(Pt 2):801–822. doi: 10.1101/sqb.1980.044.01.086. [DOI] [PubMed] [Google Scholar]
  6. Bister K., Hayman M. J., Vogt P. K. Defectiveness of avian myelocytomatosis virus MC29: isolation of long-term nonproducer cultures and analysis of virus-specific polypeptide synthesis. Virology. 1977 Oct 15;82(2):431–448. doi: 10.1016/0042-6822(77)90017-4. [DOI] [PubMed] [Google Scholar]
  7. Chiswell D. J., Ramsay G., Hayman M. J. Two virus-specific rna species are present in cells transformed by defective leukemia virus OK10. J Virol. 1981 Oct;40(1):301–304. doi: 10.1128/jvi.40.1.301-304.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Coffin J. M., Varmus H. E., Bishop J. M., Essex M., Hardy W. D., Jr, Martin G. S., Rosenberg N. E., Scolnick E. M., Weinberg R. A., Vogt P. K. Proposal for naming host cell-derived inserts in retrovirus genomes. J Virol. 1981 Dec;40(3):953–957. doi: 10.1128/jvi.40.3.953-957.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Donner P., Greiser-Wilke I., Moelling K. Nuclear localization and DNA binding of the transforming gene product of avian myelocytomatosis virus. Nature. 1982 Mar 18;296(5854):262–269. doi: 10.1038/296262a0. [DOI] [PubMed] [Google Scholar]
  10. Friedrich R., Kung H. J., Baker B., Varmus H. E., Goodman H. M., Bishop J. M. Characterization of DNA complementary to nucleotide sequences at the 5'-terminus of the avian sarcoma virus genome. Virology. 1977 Jun 1;79(1):198–215. doi: 10.1016/0042-6822(77)90345-2. [DOI] [PubMed] [Google Scholar]
  11. Graf T., Beug H. Avian leukemia viruses: interaction with their target cells in vivo and in vitro. Biochim Biophys Acta. 1978 Nov 17;516(3):269–299. doi: 10.1016/0304-419x(78)90011-2. [DOI] [PubMed] [Google Scholar]
  12. Graf T., Stéhelin D. Avian leukemia viruses. Oncogenes and genome structure. Biochim Biophys Acta. 1982 Jun 28;651(4):245–271. doi: 10.1016/0304-419x(82)90014-2. [DOI] [PubMed] [Google Scholar]
  13. Hayman M. J., Kitchener G., Graf T. Cells transformed by avian myelocytomatosis virus strain CMII contain a 90K gag-related protein. Virology. 1979 Oct 15;98(1):191–199. doi: 10.1016/0042-6822(79)90537-3. [DOI] [PubMed] [Google Scholar]
  14. Hu S. S., Moscovici C., Vogt P. K. The defectiveness of Mill Hill 2, a carcinoma-inducing avian oncovirus. Virology. 1978 Aug;89(1):162–178. doi: 10.1016/0042-6822(78)90049-1. [DOI] [PubMed] [Google Scholar]
  15. Lee J. S., Varmus H. E., Bishop J. M. Virus-specific messenger RNAs in permissive cells infected by avian sarcoma virus. J Biol Chem. 1979 Aug 25;254(16):8015–8022. [PubMed] [Google Scholar]
  16. Linial M. Two retroviruses with similar transforming genes exhibit differences in transforming potential. Virology. 1982 Jun;119(2):382–391. doi: 10.1016/0042-6822(82)90097-6. [DOI] [PubMed] [Google Scholar]
  17. Löliger H. C., Schubert H. J. Ubertragungsversuche mit aviären Myelozytomen (tumorförmige Chloroleukose, s. Chlorome) Pathol Vet. 1966;3(5):492–505. doi: 10.1177/030098586600300508. [DOI] [PubMed] [Google Scholar]
  18. McMaster G. K., Carmichael G. G. Analysis of single- and double-stranded nucleic acids on polyacrylamide and agarose gels by using glyoxal and acridine orange. Proc Natl Acad Sci U S A. 1977 Nov;74(11):4835–4838. doi: 10.1073/pnas.74.11.4835. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. Neil J. C., Breitman M. L., Vogt P. K. Characterization of a 105,000 molecular weight gag-related phosphoprotein from cells transformed by the defective avian sarcoma virus PRCII. Virology. 1981 Jan 15;108(1):98–110. doi: 10.1016/0042-6822(81)90530-4. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Ramsay G., Graf T., Hayman M. J. Mutants of avian myelocytomatosis virus with smaller gag gene-related proteins have an altered transforming ability. Nature. 1980 Nov 13;288(5787):170–172. doi: 10.1038/288170a0. [DOI] [PubMed] [Google Scholar]
  23. Ramsay G., Hayman M. J. Analysis of cells transformed by defective leukemia virus OK10: production of noninfectious particles and synthesis of Pr76gag and an additional 200,000-dalton protein. Virology. 1980 Oct 15;106(1):71–81. doi: 10.1016/0042-6822(80)90222-6. [DOI] [PubMed] [Google Scholar]
  24. Ramsay G., Hayman M. J., Bister K. Phosphorylation of specific sites in the gag-myc polyproteins encoded by MC29-type viruses correlates with their transforming ability. EMBO J. 1982;1(9):1111–1116. doi: 10.1002/j.1460-2075.1982.tb01305.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. 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]
  26. 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]
  27. Saule S., Sergeant A., Torpier G., Raes M. B., Pfeifer S., Stehelin D. Subgenomic mRNA in OK10 defective leukemia virus-transformed cells. J Virol. 1982 Apr;42(1):71–82. doi: 10.1128/jvi.42.1.71-82.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Sheiness D., Bishop J. M. DNA and RNA from uninfected vertebrate cells contain nucleotide sequences related to the putative transforming gene of avian myelocytomatosis virus. J Virol. 1979 Aug;31(2):514–521. doi: 10.1128/jvi.31.2.514-521.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Sheiness D., Fanshier L., Bishop J. M. Identification of nucleotide sequences which may encode the oncogenic capacity of avian retrovirus MC29. J Virol. 1978 Nov;28(2):600–610. doi: 10.1128/jvi.28.2.600-610.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Sheiness D., Vennstrom B., Bishop J. M. Virus-specific RNAs in cells infected by avian myelocytomatosis virus and avian erythroblastosis virus: modes of oncogene expression. Cell. 1981 Jan;23(1):291–300. doi: 10.1016/0092-8674(81)90293-2. [DOI] [PubMed] [Google Scholar]
  31. 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]
  32. Stéhelin D., Saule S., Roussel M., Sergeant A., Lagrou C., Rommens C., Raes M. B. Three new types of viral oncogenes in defective avian leukemia viruses. I. Specific nucleotide sequences of cellular origin correlate with specific transformation. Cold Spring Harb Symp Quant Biol. 1980;44(Pt 2):1215–1223. doi: 10.1101/sqb.1980.044.01.132. [DOI] [PubMed] [Google Scholar]
  33. Varmus H. E., Quintrell N., Ortiz S. Retroviruses as mutagens: insertion and excision of a nontransforming provirus alter expression of a resident transforming provirus. Cell. 1981 Jul;25(1):23–36. doi: 10.1016/0092-8674(81)90228-2. [DOI] [PubMed] [Google Scholar]
  34. Vennström B., Moscovici C., Goodman H. M., Bishop J. M. Molecular cloning of the avian myelocytomatosis virus genome and recovery of infectious virus by transfection of chicken cells. J Virol. 1981 Aug;39(2):625–631. doi: 10.1128/jvi.39.2.625-631.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Verma I. M. Genome organization of RNA tumor viruses. I. In vitro synthesis of full-genome-length single-stranded and double-stranded viral DNA transcripts. J Virol. 1978 Jun;26(3):615–629. doi: 10.1128/jvi.26.3.615-629.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES