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. 1980 Dec;77(12):7142–7146. doi: 10.1073/pnas.77.12.7142

OK10, an avian acute leukemia virus of the MC29 subgroup with a unique genetic structure

Klaus Bister *, Gary Ramsay †, Michael J Hayman †, Peter H Duesberg *
PMCID: PMC350457  PMID: 6261241

Abstract

The RNA of defective avian acute leukemia virus OK10 was isolated from a defective virus particle, released by OK10-transformed nonproducer avian fibroblasts, as a 60S complex consisting of 8.6-kilobase subunits. Oligonucleotide fingerprinting and RNA·cDNA hybridization identified two sets of sequences in OK10 RNA: group-specific sequences, which are related to all nondefective members of the avian tumor virus group, and a sequence closely related to the subgroup-specific sequences (mcv) of the myelocytomatosis virus (MC29) subgroup of avian acute leukemia viruses. Hence, OK10 is classified as a member of the MC29 subgroup of avian tumor viruses, in agreement with classification based on its oncogenic spectrum. The group-specific sequences of OK10 RNA include partial (Δ) pol and env genes, a c-region, and, unlike those of all other members of the MC29 subgroup, a complete gag gene. Oligonucleotide mapping revealed 5′-gag-Δpol-mcv-Δenv-c-3′ as the order of the subgroup-specific and group-specific elements of OK10 RNA. The genetic unit gag-Δpol-mcv, measuring ≈6.4 kilobases, codes for the nonstructural, presumably transforming, 200,000-dalton OK10-specific protein and also includes the gag gene coding for the internal virion proteins. Because gag is the only intact virion gene shared in addition to regulatory RNA sequences between OK10 and nondefective avian tumor viruses, it is concluded that the gag gene is sufficient for the formation of a defective virus particle. Comparisons among the RNAs and gene products of different viruses of the MC29 subgroup show that they share 5′-terminal gag-related and internal mcv sequences but differ from each other in intervening gag-, pol-, and mcv-related sequences. It follows that the probable transforming genes and their protein products have two essential domains, one consisting of conserved 5′ gag-related and the other of 3′ mcv-related sequence elements. In the light of this and previous knowledge we can now distinguish two designs among five different transforming onc genes of avian tumor viruses: onc genes with coding sequences unrelated to virion genes, like those of Rous sarcoma virus and avian myeloblastosis virus, and onc genes with coding sequences that are hybrids of virion genes and specific sequences, like those of the MC29 subgroup viruses, of avian erythroblastosis virus, and of Fujinami sarcoma virus.

Keywords: defective virus particle, RNA·cDNA hybridization, oligonucleotide mapping, transforming genes and proteins, two onc gene designs

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Selected References

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

  1. Beug H., von Kirchbach A., Döderlein G., Conscience J. F., Graf T. Chicken hematopoietic cells transformed by seven strains of defective avian leukemia viruses display three distinct phenotypes of differentiation. Cell. 1979 Oct;18(2):375–390. doi: 10.1016/0092-8674(79)90057-6. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Bister K., Duesberg P. H. Structure and specific sequences of avian erythroblastosis virus RNA: evidence for multiple classes of transforming genes among avian tumor viruses. Proc Natl Acad Sci U S A. 1979 Oct;76(10):5023–5027. doi: 10.1073/pnas.76.10.5023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. Bister K., Lee W. H., Duesberg P. H. Phosphorylation of the nonstructural proteins encoded by three avian acute leukemia viruses and by avian fujinami sarcoma virus. J Virol. 1980 Nov;36(2):617–621. doi: 10.1128/jvi.36.2.617-621.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bister K., Löliger H. C., Duesberg P. H. Oligoribonucleotide map and protein of CMII: detection of conserved and nonconserved genetic elements in avian acute leukemia viruses CMII, MC29, and MH2. J Virol. 1979 Oct;32(1):208–219. doi: 10.1128/jvi.32.1.208-219.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dougherty R. M., Di Stefano H. S. Virus particles associated with "nonproducer" Rous sarcoma cells. Virology. 1965 Nov;27(3):351–359. doi: 10.1016/0042-6822(65)90115-7. [DOI] [PubMed] [Google Scholar]
  8. Duesberg P. H., Bister K., Moscovici C. Avian acute leukemia virus MC29: conserved and variable RNA sequences and recombination with helper virus. Virology. 1979 Nov;99(1):121–134. doi: 10.1016/0042-6822(79)90043-6. [DOI] [PubMed] [Google Scholar]
  9. Duesberg P. H., Bister K., Moscovici C. Genetic structure of avian myeloblastosis virus, released from transformed myeloblasts as a defective virus particle. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5120–5124. doi: 10.1073/pnas.77.9.5120. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Duesberg P. H., Bister K., Vogt P. K. The RNA of avian acute leukemia virus MC29. Proc Natl Acad Sci U S A. 1977 Oct;74(10):4320–4324. doi: 10.1073/pnas.74.10.4320. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Duesberg P. H., Robinson H. L., Robinson W. S., Huebner R. J., Turner H. C. Proteins of Rous sarcoma virus. Virology. 1968 Sep;36(1):73–86. doi: 10.1016/0042-6822(68)90118-9. [DOI] [PubMed] [Google Scholar]
  12. Duesberg P. H. Transforming genes of retroviruses. Cold Spring Harb Symp Quant Biol. 1980;44(Pt 1):13–29. doi: 10.1101/sqb.1980.044.01.005. [DOI] [PubMed] [Google Scholar]
  13. Duesberg P. H., Vogt P. K. Avian acute leukemia viruses MC29 and MH2 share specific RNA sequences: evidence for a second class of transforming genes. Proc Natl Acad Sci U S A. 1979 Apr;76(4):1633–1637. doi: 10.1073/pnas.76.4.1633. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Duesberg P., Vogt P. K., Beemon K., Lai M. Avian RNA tumor viruses: mechanism of recombination and complexity of the genome. Cold Spring Harb Symp Quant Biol. 1975;39(Pt 2):847–857. doi: 10.1101/sqb.1974.039.01.099. [DOI] [PubMed] [Google Scholar]
  15. Graf T., Oker-Blom N., Todorov T. G., Beug H. Transforming capacities and defectiveness of avian leukemia viruses OK10 and E 26. Virology. 1979 Dec;99(2):431–436. doi: 10.1016/0042-6822(79)90024-2. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Hayman M. J., Royer-Pokora B., Graf T. Defectiveness of avian erythroblastosis virus: synthesis of a 75K gag-related protein. Virology. 1979 Jan 15;92(1):31–45. doi: 10.1016/0042-6822(79)90212-5. [DOI] [PubMed] [Google Scholar]
  18. Hayman M. J. Viral polyproteins in chick embryo fibroblasts infected with avian sarcoma leukosis viruses. Virology. 1978 Mar;85(1):241–252. doi: 10.1016/0042-6822(78)90428-2. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Kitchener G., Hayman M. J. Comparative tryptic peptide mapping studies suggest a role in cell transformation for the gag-related protein of avian erythroblastosis virus and avian myelocytomatosis virus strains CMII and MC29. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1637–1641. doi: 10.1073/pnas.77.3.1637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lee W. H., Bister K., Pawson A., Robins T., Moscovici C., Duesberg P. H. Fujinami sarcoma virus: an avian RNA tumor virus with a unique transforming gene. Proc Natl Acad Sci U S A. 1980 Apr;77(4):2018–2022. doi: 10.1073/pnas.77.4.2018. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Mellon P., Pawson A., Bister K., Martin G. S., Duesberg P. H. Specific RNA sequences and gene products of MC29 avian acute leukemia virus. Proc Natl Acad Sci U S A. 1978 Dec;75(12):5874–5878. doi: 10.1073/pnas.75.12.5874. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Oker-Blom N., Hortling L., Kallio A., Nurmiaho E. L., Westermarck H. OK 10 virus, an avian retrovirus resembling the acute leukaemia viruses. J Gen Virol. 1978 Sep;40(3):623–633. doi: 10.1099/0022-1317-40-3-623. [DOI] [PubMed] [Google Scholar]
  24. Oker-Blom N., Kallio A., Hortling L. Morphological changes in chick embryo cell cultures induced by avian leukosis viruses. Intervirology. 1975;5(6):342–353. doi: 10.1159/000149932. [DOI] [PubMed] [Google Scholar]
  25. Oppermann H., Bishop J. M., Varmus H. E., Levintow L. A joint produce of the genes gag and pol of avian sarcoma virus: a possible precursor of reverse transcriptase. Cell. 1977 Dec;12(4):993–1005. doi: 10.1016/0092-8674(77)90164-7. [DOI] [PubMed] [Google Scholar]
  26. Paterson B. M., Marciani D. J., Papas T. S. Cell-free synthesis of the precursor polypeptide for avian myeloblastosis virus DNA polymerase. Proc Natl Acad Sci U S A. 1977 Nov;74(11):4951–4954. doi: 10.1073/pnas.74.11.4951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. 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]
  28. 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]
  29. Scheele C. M., Hanafusa H. Proteins of helper-dependent RSV. Virology. 1971 Aug;45(2):401–410. doi: 10.1016/0042-6822(71)90341-2. [DOI] [PubMed] [Google Scholar]
  30. Wang L. H., Duesberg P., Beemon K., Vogt P. K. Mapping RNase T1-resistant oligonucleotides of avian tumor virus RNAs: sarcoma-specific oligonucleotides are near the poly(A) end and oligonucleotides common to sarcoma and transformation-defective viruses are at the poly(A) end. J Virol. 1975 Oct;16(4):1051–1070. doi: 10.1128/jvi.16.4.1051-1070.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Wang L. H. The gene order of avian RNA tumor viruses derived from biochemical analyses of deletion mutants and viral recombinants. Annu Rev Microbiol. 1978;32:561–592. doi: 10.1146/annurev.mi.32.100178.003021. [DOI] [PubMed] [Google Scholar]

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