Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1983 Feb;45(2):607–617. doi: 10.1128/jvi.45.2.607-617.1983

Recombinational junctions of variants of Moloney murine sarcoma virus: generation and divergence of a mammalian transforming gene.

D J Donoghue, T Hunter
PMCID: PMC256455  PMID: 6300424

Abstract

Different variants of Moloney murine sarcoma virus (MSV) were examined by nucleotide sequencing to compare the junctions between the acquired cellular sequence, v-mos, and the adjacent virus-derived sequences. These variants included 124-MSV, m1-MSV, and HT1-MSV and also the purportedly independent isolate Gazdar MSV. These four strains have an identical 5' junction between the murine leukemia virus env gene and the v-mos gene. This junction lies within the sixth codon of the chimeric env-mos coding region that encodes the transforming gene product. In contrast, at the 3' junction between the v-mos gene and the murine leukemia virus env gene, the three variants examined here were all different. A small deletion was found in the COOH-terminal portion of the m1-MSV env-mos coding region, indicating that the COOH terminus of this transforming gene product must be different from that of 124-MSV or HT1-MSV. The data presented here are consistent with the thesis that a virus closely related to HT1-MSV was the primordial Moloney MSV, and that all other related strains evolved from it by deletion or rearrangement. The variability observed in the Moloney MSV family is discussed in terms of possible mechanisms for the initial capture of mos sequences by the parental retrovirus and also in comparison with other transforming retrovirus families, such as Abelson murine leukemia virus and Rous sarcoma virus.

Full text

PDF

Selected References

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

  1. Aaronson S. A., Bassin R. H., Weaver C. Comparison of murine sarcoma viruses in nonproducer and S + L - -transformed cells. J Virol. 1972 Apr;9(4):701–704. doi: 10.1128/jvi.9.4.701-704.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ball J. K., Harvey D., McCarter J. A. Evidence for naturally occurring murine sarcoma virus. Nature. 1973 Jan 26;241(5387):272–275. doi: 10.1038/241272a0. [DOI] [PubMed] [Google Scholar]
  3. Ball J., McCarter J. A., Sunderland S. M. Evidence for helper independent murine sarcoma virus. I. Segregation of replication-defective and transformation-defective viruses. Virology. 1973 Nov;56(1):268–284. doi: 10.1016/0042-6822(73)90305-x. [DOI] [PubMed] [Google Scholar]
  4. Bassin R. H., Phillips L. A., Kramer M. J., Haapala D. K., Peebles P. T., Nomura S., Fischinger P. J. Transformation of mouse 3T3 cells by murine sarcoma virus: release of virus-like particles in the absence of replicating murine leukemia helper virus. Proc Natl Acad Sci U S A. 1971 Jul;68(7):1520–1524. doi: 10.1073/pnas.68.7.1520. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Blair D. G., Hull M. A., Finch E. A. The isolation and preliminary characterization of temperature-sensitive transformation mutants of Moloney sarcoma virus. Virology. 1979 Jun;95(2):303–316. doi: 10.1016/0042-6822(79)90486-0. [DOI] [PubMed] [Google Scholar]
  6. Blair D. G., McClements W. L., Oskarsson M. K., Fischinger P. J., Vande Woude G. F. Biological activity of cloned Moloney sarcoma virus DNA: Terminally redundant sequences may enhance transformation efficiency. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3504–3508. doi: 10.1073/pnas.77.6.3504. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Blair D. G., Oskarsson M., Wood T. G., McClements W. L., Fischinger P. J., Vande Woude G. G. Activation of the transforming potential of a normal cell sequence: a molecular model for oncogenesis. Science. 1981 May 22;212(4497):941–943. doi: 10.1126/science.7233190. [DOI] [PubMed] [Google Scholar]
  8. Chirigos M. A., Scott D., Turner W., Perk K. Biological, pathological and physical characterization of a possible variant of a murine sarcoma virus (Moloney). Int J Cancer. 1968 Mar 15;3(2):223–227. doi: 10.1002/ijc.2910030207. [DOI] [PubMed] [Google Scholar]
  9. Cremer K., Reddy E. P., Aaronson S. A. Translational products of Moloney murine sarcoma virus RNA: identification of proteins encoded by the murine sarcoma virus src gene. J Virol. 1981 May;38(2):704–711. doi: 10.1128/jvi.38.2.704-711.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Deng C. T., Wimmer E. Two different murine sarcoma virus isolates have homologous genome sequences: implication for their origin. Virology. 1978 Aug;89(1):309–313. doi: 10.1016/0042-6822(78)90063-6. [DOI] [PubMed] [Google Scholar]
  11. Donoghue D. J. Demonstration of biological activity and nucleotide sequence of an in vitro synthesized clone of the Moloney murine sarcoma virus mos gene. J Virol. 1982 May;42(2):538–546. doi: 10.1128/jvi.42.2.538-546.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Donoghue D. J., Hunter T. A generalized method of subcloning DNA fragments by restriction site reconstruction: application to sequencing the amino-terminal coding region of the transforming gene of Gazdar murine sarcoma virus. Nucleic Acids Res. 1982 Apr 24;10(8):2549–2564. doi: 10.1093/nar/10.8.2549. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Donoghue D. J., Hunter T. Expression of transforming region of Moloney murine sarcoma virus in Escherichia coli as a fusion protein with small tumor antigen of polyoma virus. Proc Natl Acad Sci U S A. 1982 Feb;79(3):800–804. doi: 10.1073/pnas.79.3.800. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Donoghue D. J., Sharp P. A., Weinberg R. A. Comparative study of different isolates of murine sarcoma virus. J Virol. 1979 Dec;32(3):1015–1027. doi: 10.1128/jvi.32.3.1015-1027.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Fischinger P. J., Nomura S., Peebles P. T., Haapala D. K., Bassin R. H. Reversion of murine sarcoma virus transformed mouse cells: variants without a rescuable sarcoma virus. Science. 1972 Jun 2;176(4038):1033–1035. doi: 10.1126/science.176.4038.1033. [DOI] [PubMed] [Google Scholar]
  16. Fischinger P. J., Nomura S., Tuttle-Fuller N., Dunn K. J. Revertants of mouse cells transformed by murine sarcoma virus. 3. Metastable expression of virus functions in revertants retransformed by murine sarcoma virus. Virology. 1974 May;59(1):217–229. [PubMed] [Google Scholar]
  17. Frankel A. E., Fischinger P. J. Nucleotide sequences in mouse DNA and RNA specific for Moloney sarcoma virus. Proc Natl Acad Sci U S A. 1976 Oct;73(10):3705–3709. doi: 10.1073/pnas.73.10.3705. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Gattoni S., Kirschmeier P., Weinstein I. B., Escobedo J., Dina D. Cellular Moloney murine sarcoma (c-mos) sequences are hypermethylated and transcriptionally silent in normal and transformed rodent cells. Mol Cell Biol. 1982 Jan;2(1):42–51. doi: 10.1128/mcb.2.1.42. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Gazdar A. F., Chopra H. C., Sarma P. S. Properties of a murine sarcoma virus isolated from a tumor arising in an NZW-NZB F 1 hybrid mouse. I. Isolation and pathology of tumors induced in rodents. Int J Cancer. 1972 Jan 15;9(1):219–233. [PubMed] [Google Scholar]
  20. Goff S. P., Witte O. N., Gilboa E., Rosenberg N., Baltimore D. Genome structure of Abelson murine leukemia virus variants: proviruses in fibroblasts and lymphoid cells. J Virol. 1981 May;38(2):460–468. doi: 10.1128/jvi.38.2.460-468.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hollis G. F., Hieter P. A., McBride O. W., Swan D., Leder P. Processed genes: a dispersed human immunoglobulin gene bearing evidence of RNA-type processing. Nature. 1982 Mar 25;296(5855):321–325. doi: 10.1038/296321a0. [DOI] [PubMed] [Google Scholar]
  22. Horn J. P., Wood T. G., Murphy E. C., Jr, Blair D. G., Arlinghaus R. B. A selective temperature-sensitive defect in viral RNA expression in cells infected with a ts transformation mutant of murine sarcoma virus. Cell. 1981 Jul;25(1):37–46. doi: 10.1016/0092-8674(81)90229-4. [DOI] [PubMed] [Google Scholar]
  23. Huebner R. J., Hartley J. W., Rowe W. P., Lane W. T., Capps W. I. Rescue of the defective genome of Moloney sarcoma virus from a noninfectious hamster tumor and the production of pseudotype sarcoma viruses with various murine leukemia viruses. Proc Natl Acad Sci U S A. 1966 Oct;56(4):1164–1169. doi: 10.1073/pnas.56.4.1164. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Jagadeeswaran P., Forget B. G., Weissman S. M. Short interspersed repetitive DNA elements in eucaryotes: transposable DNA elements generated by reverse transcription of RNA pol III transcripts? Cell. 1981 Oct;26(2 Pt 2):141–142. doi: 10.1016/0092-8674(81)90296-8. [DOI] [PubMed] [Google Scholar]
  25. Lenz J., Crowther R., Straceski A., Haseltine W. Nucleotide sequence of the Akv env gene. J Virol. 1982 May;42(2):519–529. doi: 10.1128/jvi.42.2.519-529.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
  27. Moloney J. B. A virus-induced rhabdomyosarcoma of mice. Natl Cancer Inst Monogr. 1966 Sep;22:139–142. [PubMed] [Google Scholar]
  28. Oskarsson M., McClements W. L., Blair D. G., Maizel J. V., Vande Woude G. F. Properties of a normal mouse cell DNA sequence (sarc) homologous to the src sequence of Moloney sarcoma virus. Science. 1980 Mar 14;207(4436):1222–1224. doi: 10.1126/science.6243788. [DOI] [PubMed] [Google Scholar]
  29. Pang R. H., Phillips L. A., Haapala D. K. Characterization of Gazdar murine sarcoma virus by nucleic acid hybridization and analysis of viral expression in cells. J Virol. 1977 Nov;24(2):551–556. doi: 10.1128/jvi.24.2.551-556.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Papkoff J., Hunter T., Beemon K. In vitro translation of virion RNA from Moloney murine sarcoma virus. Virology. 1980 Feb;101(1):91–103. doi: 10.1016/0042-6822(80)90486-9. [DOI] [PubMed] [Google Scholar]
  31. Papkoff J., Hunter T. Identification of proteins encoded by the Gazdar murine sarcoma virus genome by in vitro translation and comparison with Moloney murine sarcoma virus 124. J Virol. 1982 Aug;43(2):533–543. doi: 10.1128/jvi.43.2.533-543.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Papkoff J., Lai M. H., Hunter T., Verma I. M. Analysis of transforming gene products from Moloney murine sarcoma virus. Cell. 1981 Nov;27(1 Pt 2):109–119. doi: 10.1016/0092-8674(81)90365-2. [DOI] [PubMed] [Google Scholar]
  33. Papkoff J., Verma I. M., Hunter T. Detection of a transforming gene product in cells transformed by Moloney murine sarcoma virus. Cell. 1982 Jun;29(2):417–426. doi: 10.1016/0092-8674(82)90158-1. [DOI] [PubMed] [Google Scholar]
  34. Pragnell I. B., Fusco A., Arbuthnott C., Smadja-Joffe F., Klein B., Jasmin C., Ostertag W. Analysis of the myeloproliferative sarcoma virus genome: limited changes in the prototype lead to altered target cell specificity. J Virol. 1981 Jun;38(3):952–957. doi: 10.1128/jvi.38.3.952-957.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Reddy E. P., Smith M. J., Aaronson S. A. Complete nucleotide sequence and organization of the Moloney murine sarcoma virus genome. Science. 1981 Oct 23;214(4519):445–450. doi: 10.1126/science.6170110. [DOI] [PubMed] [Google Scholar]
  36. Shinnick T. M., Lerner R. A., Sutcliffe J. G. Nucleotide sequence of Moloney murine leukaemia virus. Nature. 1981 Oct 15;293(5833):543–548. doi: 10.1038/293543a0. [DOI] [PubMed] [Google Scholar]
  37. Todaro G. J., Aaronson S. A. Properties of clonal lines of murine sarcoma virus transformed Balb-3T3 cells. Virology. 1969 May;38(1):174–179. doi: 10.1016/0042-6822(69)90140-8. [DOI] [PubMed] [Google Scholar]
  38. Van Beveren C., Galleshaw J. A., Jonas V., Berns A. J., Doolittle R. F., Donoghue D. J., Verma I. M. Nucleotide sequence and formation of the transforming gene of a mouse sarcoma virus. Nature. 1981 Jan 22;289(5795):258–262. doi: 10.1038/289258a0. [DOI] [PubMed] [Google Scholar]
  39. Van Beveren C., van Straaten F., Galleshaw J. A., Verma I. M. Nucleotide sequence of the genome of a murine sarcoma virus. Cell. 1981 Nov;27(1 Pt 2):97–108. doi: 10.1016/0092-8674(81)90364-0. [DOI] [PubMed] [Google Scholar]
  40. Vande Woude G. F., Oskarsson M., Enquist L. W., Nomura S., Sullivan M., Fischinger P. J. Cloning of integrated Moloney sarcoma proviral DNA sequences in bacteriophage lambda. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4464–4468. doi: 10.1073/pnas.76.9.4464. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Vande Woude G. F., Oskarsson M., McClements W. L., Enquist L. W., Blair D. G., Fischinger P. J., Maizel J. V., Sullivan M. Characterization of integrated Moloney Sarcoma proviruses and flanking host sequences cloned in bacteriophage lambda. Cold Spring Harb Symp Quant Biol. 1980;44(Pt 2):735–745. doi: 10.1101/sqb.1980.044.01.079. [DOI] [PubMed] [Google Scholar]
  42. Watson R., Oskarsson M., Vande Woude G. F. Human DNA sequence homologous to the transforming gene (mos) of Moloney murine sarcoma virus. Proc Natl Acad Sci U S A. 1982 Jul;79(13):4078–4082. doi: 10.1073/pnas.79.13.4078. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Wilde C. D., Crowther C. E., Cripe T. P., Gwo-Shu Lee M., Cowan N. J. Evidence that a human beta-tubulin pseudogene is derived from its corresponding mRNA. Nature. 1982 May 6;297(5861):83–84. doi: 10.1038/297083a0. [DOI] [PubMed] [Google Scholar]
  44. Ziegler S. F., Whitlock C. A., Goff S. P., Gifford A., Witte O. N. Lethal effect of the Abelson murine leukemia virus transforming gene product. Cell. 1981 Dec;27(3 Pt 2):477–486. doi: 10.1016/0092-8674(81)90389-5. [DOI] [PubMed] [Google Scholar]

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

RESOURCES