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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1983 Jul;80(14):4408–4411. doi: 10.1073/pnas.80.14.4408

Role for the 3' end of the genome in determining disease specificity of Friend and Moloney murine leukemia viruses.

P A Chatis, C A Holland, J W Hartley, W P Rowe, N Hopkins
PMCID: PMC384047  PMID: 6308622

Abstract

To probe the genetic basis of disease specificity of nondefective murine type C viruses, we are constructing recombinants in vitro between molecular clones of Friend murine leukemia virus (Fr-MuLV) and Moloney murine leukemia virus (Mo-MuLV). Fr-MuLV induces erythroleukemias when injected into newborn NFS mice, whereas Mo-MuLV almost invariably induces T-cell lymphomas. We find that a recombinant whose genome is derived primarily from Fr-MuLV but which has 621 nucleotides of Mo-MuLV information at its 3' end induces almost exclusively thymic lymphomas. The sequences derived from Mo-MuLV include 99 nucleotides encoding the carboxyl terminus of Prp15E, the origin of DNA +-strand synthesis, all of the U3 region, and 36 nucleotides of the R portion of the long terminal repeat. When the segment of Mo-MuLV was removed and replaced with the comparable segment from Fr-MuLV, the virus was again erythroblastosis-inducing. These results, in conjunction with studies from other laboratories [Laimins, L. A., Khoury, G., Gorman, C., Howard, B. & Gruss, P. (1982) Proc. Natl. Acad. Sci. USA 79, 6453-6457], suggest that transcriptional signals in U3 may determine tissue tropism and hence influence disease specificity ("targeting") of murine leukemia viruses.

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Selected References

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  1. Aaronson S. A., Todaro G. J. Development of 3T3-like lines from Balb-c mouse embryo cultures: transformation susceptibility to SV40. J Cell Physiol. 1968 Oct;72(2):141–148. doi: 10.1002/jcp.1040720208. [DOI] [PubMed] [Google Scholar]
  2. Baltimore D. RNA-dependent DNA polymerase in virions of RNA tumour viruses. Nature. 1970 Jun 27;226(5252):1209–1211. doi: 10.1038/2261209a0. [DOI] [PubMed] [Google Scholar]
  3. Clark S. P., Mak T. W. Nucleotide sequences of the murine retrovirus Friend SFFVp long terminal repeats: identification of a structure with extensive dyad symmetry 5' to the TATA box. Nucleic Acids Res. 1982 May 25;10(10):3315–3330. doi: 10.1093/nar/10.10.3315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Faller D. V., Hopkins N. RNase T1-resistant oligonucleotides of B-tropic murine leukemia virus from BALB/c and five of its NB-tropic derivatives. J Virol. 1977 Jul;23(1):188–195. doi: 10.1128/jvi.23.1.188-195.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Gilboa E., Goff S., Shields A., Yoshimura F., Mitra S., Baltimore D. In vitro synthesis of a 9 kbp terminally redundant DNA carrying the infectivity of Moloney murine leukemia virus. Cell. 1979 Apr;16(4):863–874. doi: 10.1016/0092-8674(79)90101-6. [DOI] [PubMed] [Google Scholar]
  6. Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
  7. Green N., Shinnick T. M., Witte O., Ponticelli A., Sutcliffe J. G., Lerner R. A. Sequence-specific antibodies show that maturation of Moloney leukemia virus envelope polyprotein involves removal of a COOH-terminal peptide. Proc Natl Acad Sci U S A. 1981 Oct;78(10):6023–6027. doi: 10.1073/pnas.78.10.6023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hartley J. W., Rowe W. P. Clonal cells lines from a feral mouse embryo which lack host-range restrictions for murine leukemia viruses. Virology. 1975 May;65(1):128–134. doi: 10.1016/0042-6822(75)90013-6. [DOI] [PubMed] [Google Scholar]
  9. Jainchill J. L., Aaronson S. A., Todaro G. J. Murine sarcoma and leukemia viruses: assay using clonal lines of contact-inhibited mouse cells. J Virol. 1969 Nov;4(5):549–553. doi: 10.1128/jvi.4.5.549-553.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Laimins L. A., Khoury G., Gorman C., Howard B., Gruss P. Host-specific activation of transcription by tandem repeats from simian virus 40 and Moloney murine sarcoma virus. Proc Natl Acad Sci U S A. 1982 Nov;79(21):6453–6457. doi: 10.1073/pnas.79.21.6453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Levinson B., Khoury G., Vande Woude G., Gruss P. Activation of SV40 genome by 72-base pair tandem repeats of Moloney sarcoma virus. Nature. 1982 Feb 18;295(5850):568–572. doi: 10.1038/295568a0. [DOI] [PubMed] [Google Scholar]
  12. Linemeyer D. L., Menke J. G., Ruscetti S. K., Evans L. H., Scolnick E. M. Envelope gene sequences which encode the gp52 protein of spleen focus-forming virus are required for the induction of erythroid cell proliferation. J Virol. 1982 Jul;43(1):223–233. doi: 10.1128/jvi.43.1.223-233.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Linemeyer D. L., Ruscetti S. K., Scolnick E. M., Evans L. H., Duesberg P. H. Biological activity of the spleen focus-forming virus is encoded by a molecularly cloned subgenomic fragment of spleen focus-forming virus DNA. Proc Natl Acad Sci U S A. 1981 Mar;78(3):1401–1405. doi: 10.1073/pnas.78.3.1401. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lung M. L., Hartley J. W., Rowe W. P., Hopkins N. H. Large RNase T1-resistant oligonucleotides encoding p15E and the U3 region of the long terminal repeat distinguish two biological classes of mink cell focus-forming type C viruses of inbred mice. J Virol. 1983 Jan;45(1):275–290. doi: 10.1128/jvi.45.1.275-290.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mitra S. W., Goff S., Gilboa E., Baltimore D. Synthesis of a 600-nucleotide-long plus-strand DNA by virions of Moloney murine leukemia virus. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4355–4359. doi: 10.1073/pnas.76.9.4355. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Oliff A. I., Hager G. L., Chang E. H., Scolnick E. M., Chan H. W., Lowy D. R. Transfection of molecularly cloned Friend murine leukemia virus DNA yields a highly leukemogenic helper-independent type C virus. J Virol. 1980 Jan;33(1):475–486. doi: 10.1128/jvi.33.1.475-486.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Oliff A., Linemeyer D., Ruscetti S., Lowe R., Lowy D. R., Scolnick E. Subgenomic fragment of molecular cloned Friend murine leukemia virus DNA contains the gene(s) responsible for Friend murine leukemia virus-induced disease. J Virol. 1980 Sep;35(3):924–936. doi: 10.1128/jvi.35.3.924-936.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Robinson H. L., Blais B. M., Tsichlis P. N., Coffin J. M. At least two regions of the viral genome determine the oncogenic potential of avian leukosis viruses. Proc Natl Acad Sci U S A. 1982 Feb;79(4):1225–1229. doi: 10.1073/pnas.79.4.1225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Robinson H. L., Pearson M. N., DeSimone D. W., Tsichlis P. N., Coffin J. M. Subgroup-E avian-leukosis-virus-associated disease in chickens. Cold Spring Harb Symp Quant Biol. 1980;44(Pt 2):1133–1141. doi: 10.1101/sqb.1980.044.01.122. [DOI] [PubMed] [Google Scholar]
  20. Rowe W. P., Pugh W. E., Hartley J. W. Plaque assay techniques for murine leukemia viruses. Virology. 1970 Dec;42(4):1136–1139. doi: 10.1016/0042-6822(70)90362-4. [DOI] [PubMed] [Google Scholar]
  21. Shibuya T., Mak T. W. Host control of susceptibility to erythroleukemia and to the types of leukemia induced by Friend murine leukemia virus: initial and late stages. Cell. 1982 Dec;31(2 Pt 1):483–493. doi: 10.1016/0092-8674(82)90141-6. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Shoemaker C., Goff S., Gilboa E., Paskind M., Mitra S. W., Baltimore D. Structure of a cloned circular Moloney murine leukemia virus DNA molecule containing an inverted segment: implications for retrovirus integration. Proc Natl Acad Sci U S A. 1980 Jul;77(7):3932–3936. doi: 10.1073/pnas.77.7.3932. [DOI] [PMC free article] [PubMed] [Google Scholar]

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