Gene Transfer pp 325-361 | Cite as

Retroviral Integration and Insertional Mutagenesis

  • Stephen P. Goff


In the last decade, technology for the detection and isolation of specific genes has improved so dramatically that the DNA that encodes virtually any known protein can be obtained with modest effort and expense. Furthermore, we can manipulate cloned genes with precision, making specific alterations that might affect either coding or regulatory sequences of these genes, and we can reinstate the DNAs in cells in a functional form to assess the consequences of these alterations. Because of these technical advances, our understanding of the structural determinants of gene function has grown enormously.


Transposable Element Long Terminal Repeat Murine Leukemia Virus Insertional Mutagenesis Mouse Mammary Tumor Virus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bingham, P. M., Levis, R., and Rubin, G. M., 1981, Cloning of DNA sequences from the white locus of D. melanogaster by a novel and general method, Cell 25: 693–704.PubMedGoogle Scholar
  2. Boeke, J. D., Garfinkel, D. J., Styles, C. A., and Fink, G. R., 1985, Ty elements transpose through an RNA intermediate, Cell 40: 491–500.PubMedGoogle Scholar
  3. Boone, L. R., Myer, F. E., Yang, D. M., Ou, C.-Y., Koh, C. K., Roberson, L. E., Tennant, R. W., and Yang, W. K., 1983, Reversal of Fv-1 host range by in vitro restriction endonuclease fragment exchange between molecular clones of N-tropic and B-tropic murine leukemia virus genomes, J. Virol. 48: 110–119.PubMedGoogle Scholar
  4. Bukhari, A. L., Shapiro, J. A., and Adhya, S. L. (eds.), 1977, DNA Insertion Elements, Plasmids, and Episomes, Cold Spring Harbor Press, Cold Spring Harbor, New York.Google Scholar
  5. Canaani, E., Dreazen, O., Klar, A., Rechavi, G., Ram, D., Cohen J. B., and Givol, D., 1983, Activation of the C-mos oncogene in a mouse plasmacytoma by insertion of an endogenous intracistemal A-particle genome, Proc. Natl. Acad. Sci. U.S.A. 80: 7118–7122.PubMedGoogle Scholar
  6. Chatis, P. A., Holland, C. A., Hartley, J. W., Rowe, W. P., and Hopkins, N., 1983, Role for the 3’ end of the genome in determining disease specificity of Friend and Moloney murine leukemia viruses, Proc. Natl. Acad. Sci. U.S.A. 80: 4408–4411.PubMedGoogle Scholar
  7. Chatis, P. A., Holland, C. A., Silver, J. E., Frederickson, T. N., Hopkins, N., and Hartley, J. W., 1984, A 3’ end fragment encompassing the transcriptional enhancers of nondefective Friend virus confers erythroleukemogenicity on Moloney leukemia virus, J. Virol. 52: 248–254.PubMedGoogle Scholar
  8. Chinsky, J., and Soeiro, R., 1981, Fv-1 host restriction of Friend leukemia virus: Analysis of unintegrated proviral DNA, J. Virol. 40: 45–55.PubMedGoogle Scholar
  9. Chinsky, J., and Soeiro, R., 1982, Studies with aphidicolin on the Fv-1 restriction of Friend murine leukemia virus, J. Virol. 43: 182–190.PubMedGoogle Scholar
  10. Chiu, I.-M., Callahan, R., Tronick, S. R., Schlom, J., and Aaronson, S. A., 1984, Major pol gene progenitors in the evolution of oncoviruses, Science 223: 364–370.PubMedGoogle Scholar
  11. Cohen, J. B., Unger, T., Rechavi, G., Canaani, E., and Givol, D., 1983, Rearrangement of the oncogene c-mos in mouse myeloma NSI and hybridomas, Nature (London) 306: 797–799.Google Scholar
  12. Colicelli, J., and Goff, S. P., 1985, Mutants and pseudorevertants of Moloney murine leukemia virus with alterations at the integration site, Cell 42: 573–580.PubMedGoogle Scholar
  13. Colicelli, J., and Goff, S. P., 1986, Isolation of a recombinant murine leukemia virus utilizing a new primer tRNA, J. Virol. 57: 37–45.PubMedGoogle Scholar
  14. Ccpeland, N. G., Hutchison, K. W., and Jenkins, N. A., 1983a, Excision of the DBA ecotropic provirus in dilute coat-color revertants of mice occurs by homologous recombination involving the viral LTRs, Cell 33: 379–387.Google Scholar
  15. Copeland, N. G., Jenkins, N. A., and Lee, B. K., 1983b, Association of the lethal yellow (Ay) coat color mutation with an ecotropic murine leukemia virus genome, Proc. Natl. Acad. Sci. U.S.A. 80: 247–249.PubMedGoogle Scholar
  16. Corcoran, L. M., Adams, J. M., Dunn, A. R., and Cory, S., 1984, Murine T lymphomas in which the cellular myc oncogene has been activated by retroviral insertion, Cell 37: 113–122.PubMedGoogle Scholar
  17. Cullen, B. R., Shalka, A. M., and Ju, G., 1983, Endogenous avian retroviruses contain deficient promoter and leader sequences, Proc. Natl. Acad. Sci. U.S.A. 80: 2946–2950.PubMedGoogle Scholar
  18. Cullen, B. R., Lomedico, P. T., and Ju, G., 1984, Transcriptional interference in avian retrovirusesimplications for the promoter insertion model of leukaemogenesis, Nature (London) 307: 241–245.Google Scholar
  19. Cuypers, H. T., Selten, G., Quint, W., Zijlstra, M., Maandag, E. R., Boelens, W., van Wezenbeek, P., Melief, C., and Berns, A., 1984, Murine leukemia virus-induced T cell lymphomagenesis: Integration of proviruses in a distinct chromosomal region, Cell 37: 141–150.PubMedGoogle Scholar
  20. Decleve, A., Niwa, O., Gelmann, E., and Kaplan, H. S., 1975, Replication kinetics of N- and B-tropic murine leukemia viruses on permissive and non-permissive cells in vitro, Virology 65: 320–332.PubMedGoogle Scholar
  21. DesGroseillers, L., and Jolicoeur, P., 1983, Physical mapping of the Fv-1 tropism host range determinant of BALB/c murine leukemia viruses, J. Virol. 48: 685–696.PubMedGoogle Scholar
  22. DesGroseillers, L., Villemur, R., and Jolicoeur, P., 1984, The high leukemogenic potential of Gross passage A murine leukemia virus maps in the region of the genome corresponding to the long terminal repeat and to the 3’ end of env, J. Virol. 47: 24–32.Google Scholar
  23. Dhar, R., McClements, W. L., Enquist, L. W., and Vande Woude, G. F., 1980, Terminally repeated sequences (TRS) of integrated Moloney sarcoma provirus: Nucleotide sequence of TRS and its host and viral junctions, Proc. Natl. Acad. Sci. U.S.A. 77: 3937–3941.PubMedGoogle Scholar
  24. Dickson, C., Smith, R., Brookes, S., and Peters, G., 1984, Tumorigenesis by mouse mammary tumor virus: Proviral activation of a cellular gene in the common integration region int-2, Cell 37: 529–536.PubMedGoogle Scholar
  25. Donehower, L. A., and Varmus, H. E., 1984, A mutant murine leukemia virus with a single missense codon in pol is defective in a function affecting integration, Proc. Natl. Acad. Sci. U.S.A. 81: 6461–6465.PubMedGoogle Scholar
  26. Downward, J., Yarden, Y., Mayes, E., Scrace, G., Totty, N., Stockwell, P., Ullrich, A., Schlessinger, J., and Waterfield, M. D., 1984, Close similarity of epidermal growth factor receptor and v-erb-B oncogene protein sequences, Nature (London) 307: 521–527.Google Scholar
  27. Dunsmuir, P., Brorein, W. J., Jr., Simon, M. A., and Rubin, G. M., 1980, Insertion of the Drosophila transposable element copia generates a 5 base pair duplication, Cell 21: 575–579.PubMedGoogle Scholar
  28. Duran-Troise, G., Bassin, R. H., Rein, A., and Gerwin, B. I., 1977, Loss of Fv-1 restriction in BALB/3T3 cells following infection with a single N-tropic murine leukemia virus particle, Cell 10: 479–488.PubMedGoogle Scholar
  29. Duyk, G., Leis, J., Longiaru, M., and Skalka, A. M., 1983, Selective cleavage in the avian retroviral long terminal repeat sequence by the endonuclease associated with the alpha—beta form of avian reverse transcriptase, Proc. Natl. Acad. Sci. U.S.A. 80: 6745–6749.PubMedGoogle Scholar
  30. Etkind, P. R., and Sarkar, N. H., 1983, Integration of new endogenous mouse mammary tumor virus proviral DNA at common sites in the DNA of mammary tumors of C3Hf mice and hypomethylation of the endogenous mouse mammary tumor virus proviral DNA in C3Hf mammary tumors and spleens, J. Virol. 45: 114–123.PubMedGoogle Scholar
  31. Farabaugh, P. J., and Fink, G. R., 1980, Insertion of the eukaryotic transposable element Tyl creates a 5-base pair duplication, Nature (London) 286: 352–355.Google Scholar
  32. Fitts, R., and Temin, H. M., 1983, Cellular DNA surrounding integration sites of an avian retrovirus, J. Gen. Virol. 64: 267–274.PubMedGoogle Scholar
  33. Folger, K. R., Wong, E. A., Wahl, G., and Capecchi, M. R., 1982, Patterns of integration of DNA microinjected into cultured mammalian cells: Evidence for homologous recombination between injected plasmid DNA molecules, Mol. Cell. Biol. 2: 1372–1387.PubMedGoogle Scholar
  34. Frankel, W., Potter, T. A., Rosenberg, N., Lenz, J., and Rajan, T. V., 1985, Retroviral insertional mutagenesis of a target allele in a heterozygous murine cell line, Proc. Natl. Acad. Sci. U.S.A. 82: 6600–6604.PubMedGoogle Scholar
  35. Fung, Y.-K. T., Fadly, A. M., Crittenden, L. B., and Kung, H.-J., 1981, On the mechanism of retrovirus-induced avian lymphoid leukosis: Deletion and integration of the proviruses, Proc. Natl. Acad. Sci. U.S.A. 78: 3418–3422.PubMedGoogle Scholar
  36. Fung, Y.-K. T., Lewis, W. G., Crittenden, L. B., and Kung, H.-J., 1983, Activation of the cellular oncogene c-erbB by LTR insertion: Molecular basis for induction of erythroblastosis by avian leukosis virus, Cell 33: 357–368.PubMedGoogle Scholar
  37. Gautsch, J. W., and Wilson, M. C., 1983, Delayed de novo methylation in teratocarcinoma suggests additional tissue-specific mechanisms for controlling gene expression, Nature (London) 301: 32–37.Google Scholar
  38. Gautsch, J. W., Elder, J. H., Schindler, J., Jensen, F. C., and Lerner, R. A., 1978, Structural markers on core protein p30 of murine leukemia virus: Functional correlation with Fv-1 tropism, Proc. Natl. Acad. Sci. U.S.A. 75: 4170–4174.PubMedGoogle Scholar
  39. Gautsch, J. W., Elder, J. H., Jensen, F. C., and Lerner, R. A., 1980, In vitro construction of a B-tropic virus by recombination: B-tropism is a cryptic phenotype of xenotropic mutine retro-viruses, Proc. Natl. Acad. Sci. U.S.A. 77: 2989–2993.Google Scholar
  40. Gerwin, B. I., Rein, A., Levin, J. G., Bassin, G. H., Benjers, B. M., Kashmiri, S. V. S., Hopkins, D., and O’Neill, B. J., 1979, Mutant of B-tropic mutine leukemia virus synthesizing an altered polymerase molecule, J. Virol. 31: 741–751.PubMedGoogle Scholar
  41. Gilboa, E., Mitra, S. W., Goff, S. P., and Baltimore, D., 1979, Detailed model of reverse transcription and tests of crucial aspects, Cell 18: 93–100.PubMedGoogle Scholar
  42. Gill, R., Heffron, F., and Falkow, S., 1979, Identification of the protein encoded by the transposable element Tn3 which is required for its transposition, Nature (London) 282: 797–801.Google Scholar
  43. Goff, S. P., Traktman, P., and Baltimore, D., 1981, Isolation and properties of Moloney mutine leukemia virus: Use of a rapid assay for release of virion reverse transcriptase, J. Virol. 38: 239–248.PubMedGoogle Scholar
  44. Golomb, M., and Grandgenett, D. P., 1979, Endonuclease activity of purified RNA-directed DNA polymerase from avian myeloblastosis virus, J. Biol. Chem. 254: 1606–1613.PubMedGoogle Scholar
  45. Golomb, M., Grandgenett, D. P., and Mason, W., 1981, Virus-coded DNA endonuclease from avian retrovirus, J. Virol. 38: 548–555.PubMedGoogle Scholar
  46. Grandgenett, D. P., Vora, A. C., and Schiff, R. D., 1978, A 32,000-dalton nucleic acid binding protein from avian retrovirus cores possesses DNA endonuclease activity, Virology 89: 119–132.PubMedGoogle Scholar
  47. Hampe, A., Gobet, M., Even, J., Sherr, C. J., and Galibert, F., 1983, Nucleotide sequences of feline sarcoma virus long terminal repeats and 5’ leaders show extensive homology to those of other mammalian retroviruses, J. Virol. 45: 466–472.PubMedGoogle Scholar
  48. Harbers, K., Jahner, D., and Jaenisch, R., 1981, Microinjection of cloned retroviral genomes into mouse zygotes: Integration and expression in the animal, Nature (London) 293: 540–542.Google Scholar
  49. Harbers, K., Kuehn, M., Delius, H., and Jaenisch, R., 1984, Insertion of retrovirus into the first intron of alpha 1(I) collagen gene leads to embryonic lethal mutation in mice, Proc. Natl. Acad. Sci. U.S.A. 81: 1504–1508.PubMedGoogle Scholar
  50. Hawley, R. G., Shulman, M. J., Murialdo, H., Gibson, D. M., and Hozumi, N., 1982, Mutant immunoglobulin genes have repetitive DNA elements inserted into their intervening sequences, Proc. Natl. Acad. Sci. U.S.A. 79: 7425–7429.PubMedGoogle Scholar
  51. Hayward, W. S., Neel, B. G., and Astrin, S. M., 1981, Activation of a cellular oncogene by promoter insertion in ALV-induced lymphoid leukosis, Nature (London) 290: 475–480.Google Scholar
  52. Hizi, A., Gazit, A., Guthmann, D., and Yaniv, A., 1982, DNA-processing activities associated with the purified alpha, beta-2, and beta molecular forms of avian sarcoma virus RNA-dependent DNA polymerase, J. Virol. 41: 974–981.PubMedGoogle Scholar
  53. Hopkins, N., Schindler, J., and Hynes, R., 1977, Six NB-tropic murine leukemia viruses derived from a B-tropic virus of BALB/c have altered p30, J. Viro!. 21: 309–318.Google Scholar
  54. Hughes, S. H., Shank, P. R., Spector, D. H., Kung, H.-J., Bishop, J. M., Varmus, H. E., Vogt, P. K., and Breitman, M. L., 1978, Proviruses of avian sarcoma virus are terminally redundant, co-extensive with unintegrated linear DNA and integrated at many sites, Cell 15: 1397–1410.PubMedGoogle Scholar
  55. Hughes, S. H., Mutschler, A., Bishop, J. M., and Varmus, H. E., 1981a, A Rous sarcoma virus provirus is flanked by short direct repeats of a cellular DNA sequence present in only one copy prior to integration, Proc. Natl. Acad. Sci. U.S.A. 78: 4299–4303.PubMedGoogle Scholar
  56. Hughes, S. H., Vogt, P. K., Stubblefield, E., Bishop, J. M., and Varmus, H. E., 1981b, Integration of avian sarcoma virus DNA in chicken cells, Virology 108: 208–221.PubMedGoogle Scholar
  57. Ikenaga, H., and Saigo, S., 1982, Insertion of a movable genetic element, 297, into the TATA box for the H3 histone gene in Drosophila melanogaster, Proc. Natl. Acad. Sci. U.S.A. 79: 4143–4147PubMedGoogle Scholar
  58. Inouye, S., Yuki, S., and Saigo, K., 1984, Sequence-specific insertion of the Drosophila transposable genetic element 17.6, Nature (London) 310: 332–333.Google Scholar
  59. Jaenisch, R., 1976, Germ line integration and endogenous transmission of the exogenous Moloney murine leukemia virus, Proc. Natl. Acad. Sci. U.S.A. 73: 1260–1264.PubMedGoogle Scholar
  60. Jaenisch, R., Jahner, D., Nobis, P., Simon, I., Lohler, J., Harbers, K., and Grotkopp, D., 1981, Chromosomal position and activation of retroviral genomes inserted into the germ line of mice, Cell 24: 519–529.PubMedGoogle Scholar
  61. Jaenisch, R., Harbers, K., Schnieke, A., Lohler, J., Chumakov, I., Jahner, D., Grotkopp, D., and Hoffman, E., 1983, Germline integration of Moloney murine leukemia virus at the Mov13 locus leads to recessive lethal mutation and early embryonic death, Cell 32: 209–216.PubMedGoogle Scholar
  62. Jahner, D., Stuhlmann, H., Stewart, C. L., Harbers, K., Lohler, J., Simon, I., and Jaenisch, R., 1982, De novo methylation and expression of retroviral genomes during mouse embryogenesis, Nature (London) 298: 623–628.Google Scholar
  63. Jenkins, N. A., Copeland, N. G., Taylor, B. A., and Lee, B. K., 1981, Dilute (d) coat colour mutation of DBA/2J mice is associated with the site of integration of an ecotropic MuLV genome, Nature (London) 293: 370–374.Google Scholar
  64. Jha, K. K., Siniscalco, M., and Ozer, H. L., 1980, Temperature-sensitive mutants of BALB/3T3 cells. III. Hybrids between ts2 and other mouse mutant cells affected in DNA synthesis and correction of ts2 defects by human X chromosome, Somat. Cell Genet. 6: 603–614.PubMedGoogle Scholar
  65. Jolicoeur, P., 1979, The Fv-1 gene of the mouse and its control of murine leukemia virus replication, Curr. Top. Microbiol. Immunol. 86: 67–122.PubMedGoogle Scholar
  66. Jolicoeur, P., and Baltimore, D., 1976, Effect of Fv-1 gene product on proviral DNA formation and integration in cells infected with murine leukemia viruses, Proc. Natl. Acad. Sci. U.S.A. 73: 2236–2240.PubMedGoogle Scholar
  67. Jolicoeur, P., and Rassart, E., 1980, Effect of Fv-1 gene on product on synthesis of linear and supercoiled viral DNA in cells infected with murine leukemia virus, J. Viro!. 33: 183–195Google Scholar
  68. King, W., Patel, M. D., Lobel, L. I., Goff, S. P., and Nguyen-Huu, M. C., 1985, Insertion mutagenesis of embryonal carcinoma cells by retroviruses, Science 228: 554–558PubMedGoogle Scholar
  69. Kleckner, N., 1977, Transposable elements in procaryotes, Cell 11: 11–23.PubMedGoogle Scholar
  70. Kopchick, J. J., Harless, J., Geisser, B. S., Killam, R., Hewitt, R. R., and Arlinghaus, R. B., 1981, Endonuclease activity associated with Rauscher murine leukemia virus, J. Virol. 37: 274–283.PubMedGoogle Scholar
  71. Kriegler, M., and Botchan, M., 1983, Enhanced transformation by a simian virus 40 recombinant virus containing a Harvey murine sarcoma virus long terminal repeat, Mol. Cell. Biol. 3: 325–339.PubMedGoogle Scholar
  72. Kuff, E. L., Feenstra, A., Lueders, K., Rechavi, G., Givol, D., and Canaani, E., 1983a, Homology between an endogenous viral LTR and sequences inserted in an activated cellular oncogene, Nature (London) 302: 547–548.Google Scholar
  73. Kuff, E. L., Feenstra, A., Lueders, K., Smith, L., Hawley, R., Hozumi, N., and Shulman, M., 1983b, Intracisternal A-particle genes as movable elements in the mouse genome, Proc. Natl. Acad. Sci. U.S.A. 80: 1992–1996.PubMedGoogle Scholar
  74. Leis, J., Duyk, G., Johnson, S., Longiaru, M., and Skalka, A., 1983, Mechanism of action of the endonuclease associated with the alpha—beta and beta—beta forms of avian RNA tumor virus reverse transcriptase, J. Virol. 45: 727–739.PubMedGoogle Scholar
  75. Lemay, G., and Jolicoeur, P., 1984, Rearrangement of a DNA sequence homologous to a cell—virus junction fragment in several Moloney murine leukemia virus-induced rat thymomas, Proc. Natl. Acad. Sci. U.S.A. 81: 38–42.PubMedGoogle Scholar
  76. Lenz, J., Celander, D., Crowther, R. L., Patarca, R., Perkins, D. W., and Haseltine, W. A., 1984, Determination of the leukaemogenicity of a murine retrovirus by sequences within the long terminal repeat, Nature (London) 306: 467–470.Google Scholar
  77. Levin, J. G., Hu, S. C., Rein, A., Messer, L. I., and Gerwin, B. I., 1984, Murine leukemia virus mutant with a frameshift in the reverse transcriptase coding region: Implications for pol gene structure, J. Virol. 51: 470–478.PubMedGoogle Scholar
  78. Lilly, F., and Pincus, T., 1973, Genetic control of murine viral leukemogenesis, Adv. Cancer Res. 17: 231–277.Google Scholar
  79. Lobel, L. I., Patel, M., King, W., Nguyen-Huu, M. C., and Goff, S. P., 1985, Construction and recovery of viable retroviral genomes carrying a bacterial suppressor transfer RNA gene, Science 228: 329–332.PubMedGoogle Scholar
  80. Lohler, J., Timpl, R., and Jaenisch, R., 1984, Embryonic lethal mutation in mouse collagen I gene causes rupture of blood vessels and is associated with erythropoietic and mesenchymal cell death, Cell 38: 597–607.PubMedGoogle Scholar
  81. Luciw, P. A., Bishop, J. M., Varmus, H. E., and Capecchi, M. R., 1983, Location and function of retroviral and SV-40 sequences that enhance biochemical transformation after microinjection of DNA, Cell 33: 705–716.PubMedGoogle Scholar
  82. Luciw, P. A., Opperman, H., Bishop, J. M., and Varmus, H. E., 1984, Integration and expression of several molecular forms of Rous sarcoma virus DNA used for transfection of mouse cells, Mol. Cell. Biol. 4: 1260–1269.PubMedGoogle Scholar
  83. Majors, J. E., and Varmus, H. E., 1981, Nucleotide sequences of host—proviral junctions for mouse mammary tumour virus, Nature (London) 289: 253–258.Google Scholar
  84. Majors, J. E., and Varmus, H. E., 1983, Nucleotide sequencing of an apparent proviral copy of env mRNA defines determinants of expression of the mouse mammary tumor virus env gene, J. Virol. 47: 495–504.PubMedGoogle Scholar
  85. Misra, T. K., Grandgenett, D. P., and Parsons, J. T., 1982, Avian retrovirus pp32 DNA-binding protein. I. Recognition of specific sequences on retrovirus DNA terminal repeats, J. Virol. 44: 330–343.PubMedGoogle Scholar
  86. Mizuuchi, K., Weisberg, R., Enquist, L., Mizuuchi, M., Buraczynska, M., Foeller, C., Hsu, P.-L., Ross, W., and Landy, A., 1981, Structure and function of the phage att site: Size, int binding sites, and location of the crossover point, Cold Spring Harbor Symp. Quant. Biol. 45: 429–437.PubMedGoogle Scholar
  87. Mount, S. M., and Rubin, G. M., 1985, Complete nucleotide sequence of the Drosophila transposable element copia: Homology between copia and retroviral proteins, Mol. Cell. Biol. 5: 1630–1638.PubMedGoogle Scholar
  88. Mushinski, J. F., Potter, M., Bauer, S. R., and Reddy, E. R., 1983, DNA rearrangement and altered RNA expression of the c-myb oncogene in mouse plasmacytoid lymphosarcomas, Science 220: 795–798.PubMedGoogle Scholar
  89. Neel, B. G., Hayward, W. S., Robinson, H. L., Fang, J., and Astrin, S. M., 1981, Avian leukosis virus-induced tumors have common proviral integration sites and synthesize discrete new RNAs: Oncogenesis by promoter insertion, Cell 23: 323–334.PubMedGoogle Scholar
  90. Neil, J. C., Hughes, D., McFarlane, R., Wilkie, N. M., Onions, D. E., Lees, G., and Jarrett, O., 1984, Transduction and rearrangement of the myc gene by feline leukaemia virus in naturally-occurring T-cell leukaemias, Nature (London) 308: 814–820.Google Scholar
  91. Niwa, O., Yokota, Y., Ishida, H., and Sugahara, T., 1983, Independent mechanism involved in suppression of the Moloney murine leukemia virus genome during differentiation of murine teratocarcinoma cells, Cell 32: 1105–1113.PubMedGoogle Scholar
  92. Noori-Daloii, M. R., Swift, R. A., Kung, H. J., Crittenden, L. M., and Witter, R. L., 1981, Specific integration of REV proviruses in avian bursal lymphomas, Nature (London) 294: 574–576Google Scholar
  93. Nusse, R., and Varmus, H. E., 1982, Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome, Cell 31: 99–109.PubMedGoogle Scholar
  94. Nusse, R., van Ooyen, A., Cox, D., Fung, Y.-K. T., and Varmus, H., 1984, Mode of proviral activation of a putative mammary oncogene (int-1) on mouse chromosome 15, Nature (London) 307: 131–136.Google Scholar
  95. O’Hare, K., and Rubin, G. M., 1983, Structures of P transposable elements and their sites of insertion and excision in the Drosophila melanogaster genome, Cell 34: 25–35.PubMedGoogle Scholar
  96. Ono, M., Toh, H., Miyata, T., and Awaya, T., 1985, Nucleotide sequence of the Syrian hamster intracisternal A-particle gene: Close evolutionary relationship of type A particle gene to types B and D oncovirus genes, J. Virol. 55: 387–394.PubMedGoogle Scholar
  97. Ou, C.-Y., Boone, L. R., Koh, C.-K., Tennant, R. W., and Yang, W. K., 1983, Nucleotide sequences of gag—pol regions that determine the Fv-I host range property of BALB/c N-tropic and B-tropic murine leukemia viruses, J. Virol. 48: 779–784.PubMedGoogle Scholar
  98. Palmiter, R. D., Wilkie, T. M., Chen, H. Y., and Brinster, R. L., 1984, Transmission distortion and mosaicism in an unusual transgenic mouse pedigree, Cell 36: 869–877.PubMedGoogle Scholar
  99. Panganiban, A. T., 1985, Retroviral DNA integration, Cell 42: 5–6.PubMedGoogle Scholar
  100. Panganiban, A. T., and Temin, H. M., 1983, The terminal nucleotides of retrovirus DNA are required for integration but not virus production, Nature (London) 306: 155–160.Google Scholar
  101. Panganiban, A. T., and Temin, H. M., 1984a, Circles with two tandem LTRs are precursors to integrated retrovirus DNA, Cell 36: 673–679.PubMedGoogle Scholar
  102. Panganiban, A. T., and Temin, H. M., 1984b, The retrovirus pol gene encodes a product required for DNA integration: Identification of a retrovirus int locus, Proc. Natl. Acad. Sci. U.S.A. 81: 7885–7889.PubMedGoogle Scholar
  103. Patarca, R., and Haseltine, W. A., 1984, Sequence similarity among retroviruses, Nature (London) 306: 288.Google Scholar
  104. Payne, G. S., Courtneidge, S. A., Crittenden, L. B., Fadley, A. M., Bishop, J. M., and Vannus, H. E., 1981, Analyses of avian leukosis virus DNA and RNA in bursal tumors suggest a novel mechanism for retroviral oncogenesis, Cell 23: 311–322.PubMedGoogle Scholar
  105. Payne, G. S., Bishop, J. M., and Varmus, H. E., 1982, Multiple arrangements of viral DNA and an activated host oncogene in bursal lymphomas, Nature (London) 295: 209–214.Google Scholar
  106. Peters, G., Brookes, S., Smith, R., and Dickson, C., 1983, Tumorigenesis by mouse mammary tumor virus: Evidence for a common region for provirus integration in mammary tumors, Cell 33: 369–377.PubMedGoogle Scholar
  107. Pincus, T., Hartley, J. W., and Rowe, W. P., 1975, A major genetic locus affecting resistance to infection with murine leukemia viruses. IV. Dose—response relationships in Fv-1 sensitive and resistant cell cultures, Virology 65: 333–342.PubMedGoogle Scholar
  108. Rechavi, G., Givol, D., and Canaani, E., 1982, Activation of a cellular oncogene by DNA re- arrangement: Possible involvement of an IS-like element, Nature (London) 300: 607–610.Google Scholar
  109. Rein, A., Kashmiri, S. V. S., Bassin, R. H., Gerwin, B. I., and Duran-Troise, G., 1976, Phenotypic mixing between N- and B-tropic murine leukemia viruses: Infectious particles with dual sensitivity to Fv-1 restriction, Cell 7: 373–379.PubMedGoogle Scholar
  110. Rein, A., Gerwin, B. I., Bassin, R. H., Schwarm, L., and Schildlovsky, G., 1978, A replication-defective variant of Moloney murine leukemia virus. I. Biological characterization, J. Virol. 25: 146–156.PubMedGoogle Scholar
  111. Richter, A., Ozer, H. L., DesGroseillers, and Jolicoeur, J., 1984, An X-linked gene affecting mouse cell DNA synthesis also affects production of unintegrated linear and supercoiled DNA of murine leukemia virus, Mol. Cell. Biol. 4: 151–159.Google Scholar
  112. Roeder, G. S., and Fink, G. R., 1980, DNA rearrangements associated with a transposable element in yeast, Cell 21: 239–249.PubMedGoogle Scholar
  113. Schnieke, A., Harbers, K., and Jaenisch, R., 1983, Embryonic lethal mutation in mice induced by retrovirus insertion into the alpha 1(I) collagen gene, Nature (London) 304: 315–320.Google Scholar
  114. Schwartzberg, P., Colicelli, J., and Goff, S. P., 1984, Construction and analysis of deletion mutations in the pol gene of Moloney murine leukemia virus: A new viral function required for establishment of the integrated provirus, Cell 37: 1043–1052.PubMedGoogle Scholar
  115. Searles, L. L., Jokerst, R. S., Bingham, P. M., Voelker, R. A., and Greenleaf, A. L., 1982, Molecular cloning of sequences from a Drosophila RNA polymerase II locus by P element transposon tagging, Cell 31: 585–592.PubMedGoogle Scholar
  116. Seiki, M., Hattori, S., Hirayama, Y., and Yoshida, M., 1983, Human adult T-cell leukemia virus: Complete nucleotide sequence of the provirus genome integrated in leukemia cell DNA, Proc. Natl. Acad. Sci. U.S.A. 80: 3618–3622.PubMedGoogle Scholar
  117. Shapiro, J. A., 1979, Molecular model for the transposition and replication of bacteriophage mu and other transposable elements, Proc. Natl. Acad. Sci. U.S.A. 76: 1933–1937.PubMedGoogle Scholar
  118. Shen-Ong, G. L. C., Potter, M., Mushinski, J. F., Lavu, S., and Reddy, E. P., 1984, Activation of the c-myb locus by viral insertional mutagenesis in plasmacytoid lymphosarcomas, Science 226: 1077–1080.PubMedGoogle Scholar
  119. Shimotohno, K., Mizutani, S., and Temin, H. M., 1980, Sequence of retrovirus provirus resembles that of bacterial transposable elements, Nature (London) 285: 550–554.Google Scholar
  120. Shinnick, T. M., Lerner, R. A., and Sutcliffe, J. G., 1981, Nucleotide sequence of Moloney murine leukemia virus, Nature (London) 293: 543–548.Google Scholar
  121. Shoemaker, C., Goff, S., Gilboa, E., Paskind, M., Mitra, S. W., and Baltimore, D., 1980, Structure of a cloned circular Moloney murine leukemia virus molecule containing an inverted segment: Implications for retrovirus integration, Proc. Natl. Acad. Sci. U.S.A. 77: 3932–3936.PubMedGoogle Scholar
  122. Shoemaker, C., Goff, S., Gilboa, E., Paskind, M., Mitra, S. W., and Baltimore, D., 1981a, Structure of cloned retroviral circular DNAs: Implications for virus integration, Cold Spring Harbor Symp. Quant. Biol. 45: 711–717.PubMedGoogle Scholar
  123. Shoemaker, C., Hoffmann, J., Goff, S. P., and Baltimore, D., 1981b, Intramolecular integration within Moloney murine leukemia virus DNA, J. Virol. 40: 164–172.PubMedGoogle Scholar
  124. Silverman, S. J., and Fink, G. R., 1984, Effects of Ty insertions on HIS4 transcription in Saccharomyces cerevisiae, Mol. Cell. Biol. 4: 1246–1251.PubMedGoogle Scholar
  125. Simon, M. C., Smith, R. E., and Hayward, W. S., 1984, Mechanisms of oncogenesis by subgroup F avian leukosis viruses, J. Virol. 52: 1–8.PubMedGoogle Scholar
  126. Spradling, A. C., and Rubin, G. M., 1982, Transposition of cloned P elements into Drosophila germ line chromosomes, Science 218: 341–347.PubMedGoogle Scholar
  127. Steffen, D., 1984, Proviruses are adjacent to c-myc in some murine leukemia virus-induced lymphomas, Proc. Natl. Acad. Sci. U.S.A. 81: 2097–2101.PubMedGoogle Scholar
  128. Stewart, C. L., Stuhlmann, H., Jahner, D., and Jaenisch, R., 1982, De novo methylation, expression and infectivity of retroviral genomes introduced into embryonal carcinoma cells, Proc. Natl. Acad. Sci. U.S.A. 79: 4098–4102.PubMedGoogle Scholar
  129. Stewart, C. L., Harbers, K., Jahner, D., and Jaenisch, R., 1983, X chromosome-linked transmission and expression of retroviral genomes microinjected into mouse zygotes, Science 221: 760–762PubMedGoogle Scholar
  130. Swanstrom, R., DeLorbe, W. J., Bishop, J. M., and Varmus, H. E., 1981, Nucleotide sequence of cloned unintegrated avian sarcoma virus DNA: Viral DNA contains direct and inverted repeats similar to those in transposable elements, Proc. Natl. Acad. Sci. U.S.A. 78: 124–128PubMedGoogle Scholar
  131. Temin, H. M., 1981, Structure, variation and synthesis of retrovirus long terminal repeat, Cell 27: 1–3.PubMedGoogle Scholar
  132. Toh, H., Hayahida, H., and Miyata, T., 1983, Sequence homology between retroviral reverse transcriptase and putative polymerases of hepatitis B virus and cauliflower mosaic virus, Nature (London) 305: 827–829.Google Scholar
  133. Tsichlis, P. N., Strauss, P. G., and Hu, L. F., 1983a, A common region for proviral DNA integration in MoMuLV-induced rat thymic lymphomas, Nature (London) 302: 445–449.Google Scholar
  134. Tsichlis, P. N., Hu, L. F., and Strauss, P. G., 1983b, Two common regions for proviral DNA integration in MoMuLV-induced rat thymic lymphomas: Implications for oncogenesis, in: ICN—UCLA Symposium on Normal and Neoplastic Hematopoiesis ( D. W. Golde and P. A. Marks, eds.), pp. 399–416, Alan R. Liss, New York.Google Scholar
  135. Tsichlis, P. N., Strauss, P. G., and Kozak, C. A., 1984, Cellular DNA region involved in induction of thymic lymphomas (Mlvi-2) maps to mouse chromosome 15, Mol. Cell. Biol. 4: 997–1000.PubMedGoogle Scholar
  136. Van Beveran, C., Rands, E., Chattopadhyay, S. K., Lowy, D. R., and Verma, I. M., 1981, Long terminal repeat of murine retroviral DNAs: Sequence analysis, host—proviral junctions, and preintegration site, J. Virol. 41: 542–556.Google Scholar
  137. Van Ooyen, A, and Nusse, R., 1984, Structure and nucleotide sequence of the putative mammary oncogene int-1; proviral insertions leave the protein-encoding region intact, Cell 39: 233–240PubMedGoogle Scholar
  138. Varmus, H. E., 1983, Retroviruses, in Mobile Genetic Elements ( J. A. Shapiro, ed.), pp. 411–503, Academic Press, New York.Google Scholar
  139. Varmus, H. E., Quintell, N., and Gritz, S., 1981, Retroviruses as mutagens: Insertion and excision of a nontransfonning provirus alter expression of a resident transforming provirus, Cell 25: 23–36.PubMedGoogle Scholar
  140. Wagner, E. F., Covarrubias, L., Stewart, T. A., and Mintz, B., 1983, Prenatal lethalities in mice homozygous for human growth hormone gene sequences integrated in the germ line, Cell 35: 647–655.PubMedGoogle Scholar
  141. Wain-Hobson, S., Sonigo, P., Danos, O., Cole, S., and Alizon, M., 1985, Nucleotide sequence of the AIDS virus, LAV Cell 40: 9–17.PubMedGoogle Scholar
  142. Westaway, D., Payne, G., and Varmus, H. E., 1984, Deletions and base substitutions in provirally mutated c-myc alleles may contribute to the progression of B-cell tumors, Proc. Natl. Acad. Sci. U.S.A. 81: 843–847.PubMedGoogle Scholar
  143. Wolf, D., and Rotter, V., 1984, Inactivation of p53 gene expression by an insertion of Moloney murine leukemia virus-like DNA sequences, Mol. Cell. Biol. 4: 1402–1410.PubMedGoogle Scholar
  144. Yang, W. K., Kiggans, J. O., Yang, D., Ou, C., Tennant, R. W., Brown, A., and Bassin, R. H., 1980, Synthesis and circularization of N- and B-tropic retroviral DNA in Fv-1 permissive and restrictive mouse cells, Proc. Natl. Acad. Sci. U.S.A. 77: 2994–2998.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Stephen P. Goff
    • 1
  1. 1.Department of Biochemistry and Molecular Biophysics, College of Physicians and SurgeonsColumbia UniversityNew YorkUSA

Personalised recommendations