Skip to main content
NCBI home page
Journal of Virology logoLink to Journal of Virology
. 1983 May;46(2):337–346. doi: 10.1128/jvi.46.2.337-346.1983

Genome structure of HBI, a variant of acute leukemia virus MC29 with unique oncogenic properties.

K Bister, H W Jansen, T Graf, P Enrietto, M J Hayman
PMCID: PMC255134  PMID: 6302305

Abstract

We have analyzed the viral RNA of a variant of avian acute leukemia virus MC29, termed HBI. This virus was isolated during in vitro passage of a partially transformation-defective (td) mutant of MC29 (td10H-MC29) in chicken macrophages. While td10H-MC29 has a reduced ability to transform macrophages in vitro or to induce tumors in vivo, HBI-MC29 transforms macrophages efficiently and induces in vivo a high incidence of lymphoid tumors. Electrophoretic analysis of HBI-MC29 genomic RNA revealed that it has a complexity of 5.7 kilobases, like the RNA of wild-type (wt) MC29, and that it is 0.6 kilobases longer than the 5.1-kilobase RNA of the deletion mutant td10H-MC29. Analysis of the viral RNAs of two clonal isolates of HBI-MC29 by T1 oligonucleotide fingerprinting showed that sequences from the viral transformation-specific region, v-myc, which are deleted in td10H RNA, are present in HBI RNA. Moreover, hybridization of HBI RNA to molecularly cloned subgenomic fragments of wtMC29 proviral DNA, followed by fingerprint analysis of hybridized RNA, showed that the entire v-myc-specific RNA sequences defined previously are present. Hybridization to cloned DNA of the normal chicken locus c-myc shows a close relationship between HBI v-myc RNA and c-myc DNA, especially in the sequences which were deleted from td10H-MC29. T1 oligonucleotide maps of HBI and td10H RNAs were prepared and compared. Total conservation of the oligonucleotide pattern is observed in the overlapping v-myc regions, while the partial structural genes gag and env show some variations, most of which can be directly proven to be due to point mutations or recombination with helper viral RNAs that were analyzed in parallel. Recombination of td10H-MC29 with c-myc, followed by recombinational and mutational changes in the structural genes during passage with helper virus, could be a possible explanation for the origin of HBI.

Full text

PDF
337

Images in this article

341Image
on p.341
341Image
on p.341
342Image
on p.342
342Image
on p.342
343Image
on p.343

Selected References

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

  1. 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]
  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., 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]
  4. 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]
  5. 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]
  6. Bister K., Ramsay G. M., Hayman M. J. Deletions within the transformation-specific RNA sequences of acute leukemia virus MC29 give rise to partially transformation-defective mutants. J Virol. 1982 Mar;41(3):754–766. doi: 10.1128/jvi.41.3.754-766.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Coffin J. M., Tsichlis P. N., Barker C. S., Voynow S., Robinson H. L. Variation in avian retrovirus genomes. Ann N Y Acad Sci. 1980;354:410–425. doi: 10.1111/j.1749-6632.1980.tb27982.x. [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. Enrietto P. J., Hayman M. J. Restriction enzyme analysis of partially transformation-defective mutants of acute leukemia virus MC29. J Virol. 1982 Nov;44(2):711–715. doi: 10.1128/jvi.44.2.711-715.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. 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]
  12. Hanafusa H., Halpern C. C., Buchhagen D. L., Kawai S. Recovery of avian sarcoma virus from tumors induced by transformation-defective mutants. J Exp Med. 1977 Dec 1;146(6):1735–1747. doi: 10.1084/jem.146.6.1735. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lautenberger J. A., Schulz R. A., Garon C. F., Tsichlis P. N., Papas T. S. Molecular cloning of avian myelocytomatosis virus (MC29) transforming sequences. Proc Natl Acad Sci U S A. 1981 Mar;78(3):1518–1522. doi: 10.1073/pnas.78.3.1518. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Mladenov Z., Heine U., Beard D., Beard J. W. Strain MC29 avian leukosis virus. Myelocytoma, endothelioma, and renal growths: pathomorphological and ultrastructural aspects. J Natl Cancer Inst. 1967 Mar;38(3):251–285. [PubMed] [Google Scholar]
  15. Neel B. G., Gasic G. P., Rogler C. E., Skalka A. M., Ju G., Hishinuma F., Papas T., Astrin S. M., Hayward W. S. Molecular analysis of the c-myc locus in normal tissue and in avian leukosis virus-induced lymphomas. J Virol. 1982 Oct;44(1):158–166. doi: 10.1128/jvi.44.1.158-166.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Ramsay G. M., Enrietto P. J., Graf T., Hayman M. J. Recovery of myc-specific sequences by a partially transformation-defective mutant of avian myelocytomatosis virus, MC29, correlates with the restoration of transforming activity. Proc Natl Acad Sci U S A. 1982 Nov;79(22):6885–6889. doi: 10.1073/pnas.79.22.6885. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Ramsay G. M., Hayman M. J. Isolation and biochemical characterization of partially transformation-defective mutants of avian myelocytomatosis virus strain MC29: localization of the mutation to the myc domain of the 110,000-dalton gag-myc polyprotein. J Virol. 1982 Mar;41(3):745–753. doi: 10.1128/jvi.41.3.745-753.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  19. 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]
  20. Robins T., Bister K., Garon C., Papas T., Duesberg P. Structural relationship between a normal chicken DNA locus and the transforming gene of the avian acute leukemia virus MC29. J Virol. 1982 Feb;41(2):635–642. doi: 10.1128/jvi.41.2.635-642.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. Takeya T., Hanafusa H. DNA sequence of the viral and cellular src gene of chickens. II. Comparison of the src genes of two strains of avian sarcoma virus and of the cellular homolog. J Virol. 1982 Oct;44(1):12–18. doi: 10.1128/jvi.44.1.12-18.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Vennstrom B., Sheiness D., Zabielski J., Bishop J. M. Isolation and characterization of c-myc, a cellular homolog of the oncogene (v-myc) of avian myelocytomatosis virus strain 29. J Virol. 1982 Jun;42(3):773–779. doi: 10.1128/jvi.42.3.773-779.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Wang L. H., Duesberg P. H., Robins T., Yokota H., Vogt P. K. The terminal oligonucleotides of avian tumor virus RNAs are genetically linked. Virology. 1977 Oct 15;82(2):472–492. doi: 10.1016/0042-6822(77)90020-4. [DOI] [PubMed] [Google Scholar]
  25. Wang L. H., Halpern C. C., Nadel M., Hanafusa H. Recombination between viral and cellular sequences generates transforming sarcoma virus. Proc Natl Acad Sci U S A. 1978 Dec;75(12):5812–5816. doi: 10.1073/pnas.75.12.5812. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES