Abstract
The biological consequences of radiation leukemia virus (RadLV) infection include the stimulation of H-2Dd antigen expression in resistant mouse strains and thymoma induction in susceptible strains. In an effort to understand the genetic basis of these phenomena, the integrated ecotropic RadLV genome has been examined in a number of primary RadLV-induced tumors, as well as thymomas adapted to in vitro passage; considerable heterogeneity was observed. Examination of these polymorphic viral sequences should help define the viral gene(s) involved in the biological effects of RadLV infection; toward this end, integrated RadLV genomes were molecularly cloned and examined. The genomes and their flanking sequence were characterized by restriction enzyme analysis. Three unique viral genomes were obtained which represent four integration sites. The three RadLV genomes are shown to carry polymorphisms of the original tumor. Following DNA transfection, one of the three genomes replicated in and reinfected both mouse thymocytes and fibroblasts, but not mink fibroblasts in vitro. Virus encoded by the other two DNA genomes could not be recovered following transfection into any of the three cell types. One of these two apparently defective retroviruses encodes a truncated p15E molecule, while the other has elongated long terminal repeats (LTRs). The non-defective ecotropic isolate was collected from in vitro tissue culture supernatants, concentrated, and used to infect mice. Thymocytes of infected, resistant mice were shown to express elevated levels of H-2Dd antigen as early as 12 days post infection, a hallmark of RadLV infection.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bach, R. G. and Meruelo, D.: Identtification of a 36,000-molecular weight, gag-related phosphoprotein in lymphoma cells transformed by radiation leukemia virus.J Exp Med 160: 270–285, 1984
Bieberich, C., Scangos, G., Tanaka, K., and Jay, G.: Regulated expression of a murine class I gene in transgenic mice.Mol Cell Biol 6: 1339–1342, 1986
Blin, N. and Stafford, D. W.: Isolation of high molecular-weight DNA.Nucleic Acids Res 3: 2303–2308, 1976
Brown, G. D., Choi, Y., Pampeno, C., and Meruelo, D.: Regulation ofH-2 class I gene expression in virally transformed and infected cells.CRC Crit Rev Immunol 8: 175–215, 1988a
Brown, G. D., Choi, Y., Egan, G., and Meruelo, D.: Extension of the H-2 TLb molecular map. Isolation and characterization ofT13, T14, andT15 from the C57BL/6 mouse.Immunogenetics 27: 239–251, 1988b
Carle, G. F., Frank, M., and Olson, M. V.: Electrophoretic separations of large DNA molecules by periodic inversion of the electric field.Science 232: 65–68, 1986
Chan, H. W., Bryan, T., Moore, J. L., Staal, S. P., Rowe, W. P., and Martin, M. A.: Identification of ecotropic proviral sequences in inbred mouse strains with a cloned subgenomic DNA fragment.Proc Natl Acad Sci USA 77: 5779–5783, 1980
Chattopadhyay, S. K., Lander, M. R., Rands, E., and Lowy, D. R.: Structure of endogenous murine leukemia virus DNA in mouse genomes.Proc Natl Acad Sci USA 77: 5774–5778, 1980
Chattopadhyay, S. K., Cloyd, M. W., Linemeyer, D. L., Lander, M. R., Rands, E., and Lowy, D. R.: Cellular origin and role of mink cell focus-forming viruses in murine thymic lymphomas.Nature 295: 25–31, 1982
DesGroseillers, L. and Jolicoeur, P.: The tandem direct repeats within the long terminal repeat of murine leukemia viruses are the primary determinant of their leukemogenic potential.J Virol 52: 945–952, 1984
Dinces, N. B. and Milman, G.: Encapsidation and expression of the herpes thymidine kinase gene in polyoma virus.J Virol 42: 691–699, 1982
Gough, N. M., Gough, J., Metcalf, D., Kelso, A., Grail, D., Nicola, N. A., Burgess, A. W., and Dunn, A. R.: Molecular cloning of cDNA encoding a murine haematopoietic growth regulator, granulocyte-macrophage colony stimulating factor.Nature 309: 763–767, 1984
Graham, F. L. and van der Eb, A. J.: A new technique for the assay of infectivity of human adenovirus 5 DNA.Virology 52: 456–467, 1973
Gross, L.: Attempt to recover filterable agent from x-ray-induced leukemia.Acta Haematol (Basel) 19: 353–361, 1958
Grosveld, F. G., Lund, T., Murray, E. J., Mellor, A. L., Dahl, H. H. M., and Flavell, R. A.: The construction of cosmid libraries which can be used to transform eukaryotic cells.Nucleic Acids Res 10: 6715–6732, 1982
Hanahan, D. and Meselson, M.: Plasmid screening at high colony density.Gene 10: 63–67, 1980
Hartley, J. W. and Rowe, W. P.: Clonal cell lines from a feral mouse embryo which lack host-range restrictions for murine leukemia viruses.Virology 65: 128–134, 1975
Holland, C. A., Hartley, J. W., Rowe, W. P., and Hopkins, N.: At least four viral genes contribute to the leukemogenicity of murine retrovirus MCF 247 in AKR mice.J Virol 53: 158–165, 1985
Janowski, M., Merregaert, J., Boniver, J., and Maisin, J. R.: Proviral genome of radiation leukemia virus: molecular cloning of biologically active proviral DNA and nucleotide sequence of its long terminal repeat.J Virol 55: 251–255, 1985
Kaplan, H. S.: On the natural history of the murine leukemias.Cancer Res 27: 1325–1340, 1967
Kaplan, H. S. and Brown, M. B.: A quantitative dose response study of lymphoid tumor development in irradiated C57 black mice.J Natl Cancer Inst 13: 185–208, 1952
Lieberman, M. and Kaplan, H. S.: Leukemogenic activity of filtrates from radiation-induced lymphoid tumors of mice.Science 130: 387–388, 1959
Lieberman, M., Decleve, A., Ricciardi-Castagnoli, P., Boniver, J., Finn, O. J., and Kaplan, H. S.: Establishment, characterization and virus expression of cell lines derived from radiation-and virus-induced lymphomas of C57BL/Ka mice.Int J Cancer 24: 168–177, 1979
Loenen, W. A. and Brammar, W. J.: A bacteriophage lambda vector for cloning large DNA fragments made with several restriction enzymes.Gene 10: 249–259, 1980
Lowy, D. R., Rands, E., Chattopadhyay, S. K., Garon, C. F., and Hager, G. L.: Molecular cloning of infectious integrated murine leukemia virus DNA from infected mouse cells.Proc Natl Acad Sci USA 77: 614–618, 1980
Maniatis, T., Fritsch, E. F., and Sambrook, J.:Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, 1982
McGrath, M., Witte, O., Pincus, T., and Weissman, I. L.: Retrovirus purification: a method that conserves envelope glycoprotein and maximizes infectivity.J Virol 25: 923–927, 1978
Meruelo, D.: A role for elevated H-2 antigen expression in resistance to neoplasia caused by radiation-induced leukemia virus.J Exp Med 149: 898–909, 1979
Meruelo, D., Lieberman, M., Ginzton, N., Deuk, B., and McDevitt, H. O.: Genetic control of radiation leukemia virus-induced tumorigenesis.J Exp Med 146: 1079–1087, 1977
Meruelo, D., Nimelstein, S. H., Jones, P. P., Lieberman, M., and McDevitt, H. O.: Increased synthesis and expression of H-2 antigens on thymocytes as a result of radiation leukemia virus infection.J Exp Med 147: 470–487, 1978
Meruelo, D., Kornreich, R., Rossomando, A., Pampeno, C., Boral, A., Silver, J. L., Buxbaum, J., Weiss, E. H., Devlin, J. J., Mellor, A. L., Flavell, R. A., and Pellicer, A.: Lack of class I H-2 antigens in cells transformed by radiation leukemia virus is associated with methylation and rearrangement of H-2 DNA.Proc Natl Acad Sci USA 83: 4504–4508, 1986
Nusse, R.: Proviral activation of int-1 in mammary tumors.In K. Lapis and S. Eckhardt (eds.):Lectures and Symposia of the 14th International Congress, Akademiai Kiado, Budapest, 1987
Okumura, K., Herzenberg, L. A.: Murphy, D. B., McDevitt, H. O., and Herzenberg, L. A.: Selective expression ofH-2 (I region) loci controlling determinants on helper and suppressor T lymphocytes.J Exp Med 144: 685–698, 1976
Pampeno, C. L. and Meruelo, D.: Isolation of a retroviruslike sequence from theTL locus of the C57BL/10 murine MHC.J Virol 58: 296–306, 1986
Rassart, E., Sankar-Mistry, P., Lemay, G., DesGroseillers, L., and Jolicoeur, P.: New class of leukemogenic ecotropic recombinant murine leukemia virus isolated from radiation-induced thymomas of C57BL/6 mice.J Virol 45: 565–575, 1983
Rassart, E., Shang, M., Boie, Y., and Jolicoeur, P.: Studies on emerging radiation leukemia virus varients in C57BL/Ka mice.J Virol 58: 96–106, 1986
Schrier, P. I., Bernards, R., Vaessen, R. T. M. J., Houweling, A., and van der Eb, A. J.: Expression of class I MHC antigens switched off by highly oncogenic adenovirus 12 in transformed rat cells.Nature 305: 771–775, 1983
Shelton, D. L. and Reichardt, L. F.: Expression of the beta-nerve growth factor gene correlates with the density of sympathetic innervation in effector organs.Proc Natl Acad Sci USA 81: 7951–7955, 1984
Sithanandam, G. and Rapp, U. R.: A single point mutation in the envelope gene is responsible for replication and XC fusion deficiency of the endogenous ecotropic C3H/He murine leukemia virus and for its repair in culture.J Virol 62: 932–943, 1988
Stephenson, J. R., Reynolds, R. K., and Aaronson, S. A.: Isolation of temperature-sensitive mutants of murine leukemia virus.Virology 48: 749–756, 1972
Swan, D. C., McBride, O. W., Robbins, K. C., Keithley, D. A., Reddy, E. P., and Aaronson, S. A.: Chromosomal mapping of the simian sarcoma virusonc gene analog in human cells.Proc Natl Acad Sci USA 79: 4691–4695, 1982
Tamaka, K., Isselbacher, K. J., Khoury, G., and Jay, G.: Reversal of oncogenesis by the expression of a MHC class I gene.Science 228: 26–30, 1985
Villemur, R., Rassart, E., DesGroseillers, L., and Jolicoeur, P.: Molecular cloning of viral DNA from leukemogenic Gross passage A murine leukemia virus and nucleotide sequence of its long terminal repeat.J Virol 45: 539–546, 1983
Yang, F., Lum, J. B., McGill, J. R., Moore, C. M., Naylor, S. L., van Bragt, P. H., Baldwin, W. D., and Bowman, B. H.: Human transferrin: cDNA characterization and chromosomal localization.Proc Natl Acad Sci USA 81: 2752–2756, 1984
Author information
Authors and Affiliations
Additional information
Offprint requests to: G. D. Brown.
Rights and permissions
About this article
Cite this article
Brown, G.D., Egan, G., Dowling, T. et al. Increased H-2Dd expression following infection by a molecularly cloned ecotropic MuLV. Immunogenetics 31, 94–103 (1990). https://doi.org/10.1007/BF00661219
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00661219