Abstract
SL3-3 is a potent leukemogenic retrovirus that closely resembles the non-leukemogenic virus Akv. Both viruses were isolated from AKR mice, have ecotropic host ranges, and form plaques in the XC assay. They differ at only 1 to 2% of the nucleotides in the viral genomes but differ markedly in virulence properties. SL3-3 induces leukemia in a high percentage of inoculated AKR, C3H, CBA, and NFS mice, whereas Akv does not induce disease in any of these strains. To determine which region of the genome accounts for the leukemogenic potential of SL3-3, we constructed recombinant genomes between molecular clones of SL3-3 and Akv. Recombinant, viral DNA genomes were cloned and then were transfected onto NIH 3T3 fibroblasts to generate infectious virus. The recombinant viruses were tested for leukemogenicity in AKR/J, CBA/J, and C3Hf/Bi mice. We localized the primary leukemogenic determinant to a 3.8-kilobase fragment of the SL3-3 genome containing the viral long terminal repeat, 5' untranslated sequences, gag gene, and 5', 30% of the pol gene. Reciprocal recombinants containing the equivalent region from Akv, linked to the env gene and the remainder of the pol gene from SL3-3, did not induce leukemia. We conclude that the primary virulence determinant of SL3-3 lies outside the region of the genome that encodes the envelope proteins gp70 and p15E.
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Selected References
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- Buchhagen D. L., Pedersen F. S., Crowther R. L., Haseltine W. A. Most sequence differences between the genomes of the Akv virus and a leukemogenic Gross A virus passaged in vitro are located near the 3' terminus. Proc Natl Acad Sci U S A. 1980 Jul;77(7):4359–4363. doi: 10.1073/pnas.77.7.4359. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chattopadhyay S. K., Cloyd M. W., Linemeyer D. L., Lander M. R., Rands E., Lowy D. R. Cellular origin and role of mink cell focus-forming viruses in murine thymic lymphomas. Nature. 1982 Jan 7;295(5844):25–31. doi: 10.1038/295025a0. [DOI] [PubMed] [Google Scholar]
- Chattopadhyay S. K., Lander M. R., Gupta S., Rands E., Lowy D. R. Origin of mink cytopathic focus-forming (MCF) viruses:comparison with ecotropic and xenotropic murine leukemia virus genomes. Virology. 1981 Sep;113(2):465–483. doi: 10.1016/0042-6822(81)90175-6. [DOI] [PubMed] [Google Scholar]
- Cloyd M. W. Characterization of target cells for MCF viruses in AKR mice. Cell. 1983 Jan;32(1):217–225. doi: 10.1016/0092-8674(83)90512-3. [DOI] [PubMed] [Google Scholar]
- Cloyd M. W., Hartley J. W., Rowe W. P. Lymphomagenicity of recombinant mink cell focus-inducing murine leukemia viruses. J Exp Med. 1980 Mar 1;151(3):542–552. doi: 10.1084/jem.151.3.542. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Copeland N. G., Cooper G. M. Transfection by exogenous and endogenous murine retrovirus DNAs. Cell. 1979 Feb;16(2):347–356. doi: 10.1016/0092-8674(79)90011-4. [DOI] [PubMed] [Google Scholar]
- Dugaiczyk A., Boyer H. W., Goodman H. M. Ligation of EcoRI endonuclease-generated DNA fragments into linear and circular structures. J Mol Biol. 1975 Jul 25;96(1):171–184. doi: 10.1016/0022-2836(75)90189-8. [DOI] [PubMed] [Google Scholar]
- Famulari N. G., Buchhagen D. L., Klenk H. D., Fleissner E. Presence of murine leukemia virus envelope proteins gp70 and p15(E) in a common polyprotein of infected cells. J Virol. 1976 Nov;20(2):501–508. doi: 10.1128/jvi.20.2.501-508.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Famulari N. G., English K. J. Env gene products of AKR dual-tropic viruses: examination of peptide maps and cell surface expression. J Virol. 1981 Dec;40(3):971–976. doi: 10.1128/jvi.40.3.971-976.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hartley J. W., Wolford N. K., Old L. J., Rowe W. P. A new class of murine leukemia virus associated with development of spontaneous lymphomas. Proc Natl Acad Sci U S A. 1977 Feb;74(2):789–792. doi: 10.1073/pnas.74.2.789. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Herr W., Corbin V., Gilbert W. Nucleotide sequence of the 3' half of AKV. Nucleic Acids Res. 1982 Nov 11;10(21):6931–6944. doi: 10.1093/nar/10.21.6931. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Holmes D. S., Quigley M. A rapid boiling method for the preparation of bacterial plasmids. Anal Biochem. 1981 Jun;114(1):193–197. doi: 10.1016/0003-2697(81)90473-5. [DOI] [PubMed] [Google Scholar]
- Hoopes B. C., McClure W. R. Studies on the selectivity of DNA precipitation by spermine. Nucleic Acids Res. 1981 Oct 24;9(20):5493–5504. doi: 10.1093/nar/9.20.5493. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kalyanaraman V. S., Sarngadharan M. G., Nakao Y., Ito Y., Aoki T., Gallo R. C. Natural antibodies to the structural core protein (p24) of the human T-cell leukemia (lymphoma) retrovirus found in sera of leukemia patients in Japan. Proc Natl Acad Sci U S A. 1982 Mar;79(5):1653–1657. doi: 10.1073/pnas.79.5.1653. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Karshin W. L., Arcement L. J., Naso R. B., Arlinghaus R. B. Common precursor for Rauscher leukemia virus gp69/71, p15(E), and p12(E). J Virol. 1977 Sep;23(3):787–798. doi: 10.1128/jvi.23.3.787-798.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lee J. C., Ihle J. N. Chronic immune stimulation is required for Moloney leukaemia virus-induced lymphomas. Nature. 1981 Jan 29;289(5796):407–409. doi: 10.1038/289407a0. [DOI] [PubMed] [Google Scholar]
- Lee J. C., Ihle J. N. Increased responses to lymphokines are correlated with preleukemia in mice inoculated with Moloney leukemia virus. Proc Natl Acad Sci U S A. 1981 Dec;78(12):7712–7716. doi: 10.1073/pnas.78.12.7712. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lenz J., Crowther R., Klimenko S., Haseltine W. Molecular cloning of a highly leukemogenic, ecotropic retrovirus from an AKR mouse. J Virol. 1982 Sep;43(3):943–951. doi: 10.1128/jvi.43.3.943-951.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Lowy D. R., Rands E., Chattopadhyay S. K., Garon C. F., Hager G. L. Molecular cloning of infectious integrated murine leukemia virus DNA from infected mouse cells. Proc Natl Acad Sci U S A. 1980 Jan;77(1):614–618. doi: 10.1073/pnas.77.1.614. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Lung M. L., Hering C., Hartley J. W., Rowe W. P., Hopkins N. Analysis of the genomes of mink cell focus-inducing murine type-C viruses: a progress report. Cold Spring Harb Symp Quant Biol. 1980;44(Pt 2):1269–1274. doi: 10.1101/sqb.1980.044.01.138. [DOI] [PubMed] [Google Scholar]
- Naso R. B., Arcement L. J., Karshin W. L., Jamjoom G. A., Arlinghaus R. B. A fucose-deficient glycoprotein precursor to Rauscher leukemia virus gp69/71. Proc Natl Acad Sci U S A. 1976 Jul;73(7):2326–2330. doi: 10.1073/pnas.73.7.2326. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nowinski R. C., Hays E. F. Oncogenicity of AKR endogenous leukemia viruses. J Virol. 1978 Jul;27(1):13–18. doi: 10.1128/jvi.27.1.13-18.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
- O'Donnell P. V., Stockert E., Obata Y., Old L. J. Leukemogenic properties of AKR dualtropic (MCF) viruses: amplification of murine leukemia virus-related antigens on thymocytes and acceleration of leukemia development in AKR mice. Virology. 1981 Jul 30;112(2):548–563. doi: 10.1016/0042-6822(81)90301-9. [DOI] [PubMed] [Google Scholar]
- Pedersen F. S., Crowther R. L., Hays E. F., Nowinski R. C., Haseltine W. A. Structure of retroviral RNAs produced by cell lines derived from spontaneous lymphomas of AKR mice. J Virol. 1982 Jan;41(1):18–29. doi: 10.1128/jvi.41.1.18-29.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pedersen F. S., Crowther R. L., Tenney D. Y., Reimold A. M., Haseltine W. A. Novel leukaemogenic retroviruses isolated from cell line derived from spontaneous AKR tumour. Nature. 1981 Jul 9;292(5819):167–170. doi: 10.1038/292167a0. [DOI] [PubMed] [Google Scholar]
- Pedersen F. S., Haseltine W. A. Analysis of the genome of an endogenous, ecotropic retrovirus of the AKR strain of mice: micromethod for detailed characterization of high-molecular-weight RNA. J Virol. 1980 Jan;33(1):349–365. doi: 10.1128/jvi.33.1.349-365.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pinter A., Fleissner E. The presence of disulfide-linked gp70-p15(E) complexes in AKR murine leukemia virus. Virology. 1977 Dec;83(2):417–422. doi: 10.1016/0042-6822(77)90187-8. [DOI] [PubMed] [Google Scholar]
- Poiesz B. J., Ruscetti F. W., Gazdar A. F., Bunn P. A., Minna J. D., Gallo R. C. Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7415–7419. doi: 10.1073/pnas.77.12.7415. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Quint W., Quax W., van der Putten H., Berns A. Characterization of AKR murine leukemia virus sequences in AKR mouse substrains and structure of integrated recombinant genomes in tumor tissues. J Virol. 1981 Jul;39(1):1–10. doi: 10.1128/jvi.39.1.1-10.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rapp U. R. Kinetics of expression of infectious ecotropic, xenotropic, and mink cell focus-forming murine leukemia virus after 5-iododeoxyuridine induction of cells from high- and low-leukemia mouse strains. J Virol. 1983 Feb;45(2):755–765. doi: 10.1128/jvi.45.2.755-765.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rapp U. R., Todaro G. J. Generation of oncogenic type C viruses: rapidly leukemogenic viruses derived from C3H mouse cells in vivo and in vitro. Proc Natl Acad Sci U S A. 1978 May;75(5):2468–2472. doi: 10.1073/pnas.75.5.2468. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Reitz M. S., Jr, Poiesz B. J., Ruscetti F. W., Gallo R. C. Characterization and distribution of nucleic acid sequences of a novel type C retrovirus isolated from neoplastic human T lymphocytes. Proc Natl Acad Sci U S A. 1981 Mar;78(3):1887–1891. doi: 10.1073/pnas.78.3.1887. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Rowe W. P., Cloyd M. W., Hartley J. W. Status of the association of mink cell focus-forming viruses with leukemogenesis. Cold Spring Harb Symp Quant Biol. 1980;44(Pt 2):1265–1268. doi: 10.1101/sqb.1980.044.01.137. [DOI] [PubMed] [Google Scholar]
- Roy-Burman P., Dougherty M., Pal B. K., Charman H. P., Klement V., Gardner M. B. Assay for type C virus in mouse sera based on particulate reverse transcriptase activity. J Virol. 1976 Sep;19(3):1107–1110. doi: 10.1128/jvi.19.3.1107-1110.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Temin H. M. Function of the retrovirus long terminal repeat. Cell. 1982 Jan;28(1):3–5. doi: 10.1016/0092-8674(82)90367-1. [DOI] [PubMed] [Google Scholar]
- Temin H. M. Structure, variation and synthesis of retrovirus long terminal repeat. Cell. 1981 Nov;27(1 Pt 2):1–3. doi: 10.1016/0092-8674(81)90353-6. [DOI] [PubMed] [Google Scholar]
- Thomas C. Y., Coffin J. M. Genetic alterations of RNA leukemia viruses associated with the development of spontaneous thymic leukemia in AKR/J mice. J Virol. 1982 Aug;43(2):416–426. doi: 10.1128/jvi.43.2.416-426.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yoshimura F. K., Breda M. Lack of AKR ecotropic provirus amplification in AKR leukemic thymuses. J Virol. 1981 Sep;39(3):808–815. doi: 10.1128/jvi.39.3.808-815.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]