Papillomavirus Cloning Vectors

  • Daniel DiMaio
Part of the The Viruses book series (VIRS)


The papillomaviruses are proving to be valuable tools for transferring genes into living mammalian cells because the viral DNA can be used to establish permanent cell lines containing the transferred genes as unrearranged, extrachromosomal DNA molecules. This use of these viruses may help elucidate the function and regulation of eukaryotic genes and may enable the production of gene products that would otherwise be difficult to obtain. Bovine papillomavirus type 1 is the only papillomavirus to be exploited so far as a cloning vector, but it is likely that similar vectors will also be derived from DNA of other papillomaviruses.


C127 Cell Mouse Cell Mouse Mammary Tumor Virus Virus Surface Antigen Vesicular Stomatitis Virus Glycoprotein 
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  1. Alexander, J., Bey, E. M., Geddes, E. W., and Lecatsas, G., 1976, Establishment of a continuously growing cell line from primary carcinoma of the liver, S. Afr. Med. J. 50: 2124–2128.PubMedGoogle Scholar
  2. Amtmann, E., and Sauer, G., 1982, Bovine papillomavirus transcription: Polyadenylated RNA species and assessment of the direction of transcription, J. Virol. 43: 59–66.PubMedGoogle Scholar
  3. Binetruy, B., Meneguzzi, G., Breathnach, R., and Cuzin, F., 1982, Recombinant DNA molecules comprising bovine papilloma virus type 1 DNA linked to plasmid DNA are maintained in a plasmidial state both in rodent fibroblasts and in bacterial cells, EMBO J. 1: 621–628.PubMedGoogle Scholar
  4. Black, P. H., Hartley, J. W., Rowe, W. P., and Heubner, R. J., 1963, Transformation of bovine tissue cells by bovine papillomavirus, Nature 199: 1016–1018.PubMedCrossRefGoogle Scholar
  5. Breathnach, R., 1984, Selective amplification in methotrexate-resistant mouse cells of an artificial dihydrofolate reductase transcription unit making use of cryptic splicing and polyadenylation sites, EMBO J. 3: 901–908.PubMedGoogle Scholar
  6. Breitman, M. L., Tsui, L.-C., Buchwald, M., and Siminovitch, L., 1982, Introduction and recovery of a selectable bacterial gene from the genome of mammalian cells, Mol. Cell. Biol. 2: 966–976.PubMedGoogle Scholar
  7. Campo, M. S., 1985, Bovine papillomavirus DNA: A eukaryotic cloning vector, in: DNA Cloning: A Practical Approach (D. Glover, ed. ), IRL Press.Google Scholar
  8. Campo, M. S., and Spandidos, D. A., 1983, Molecularly cloned bovine papillomavirus DNA transforms mouse fibroblasts in vitro, J. Gen. Virol. 64: 549–557.PubMedCrossRefGoogle Scholar
  9. Canaani, D., and Berg, P., 1982, Regulated expression of the human beta 1 interferon gene after transduction into cultured mouse and rabbit cells, Proc. Natl. Acad. Sci. USA 79: 5166–5170.PubMedCrossRefGoogle Scholar
  10. Cepko, C. L., Roberts, B. E., and Mulligan, R. C., 1984, Construction and applications of a highly transmissible murine retrovirus shuttle vector, Cell 37: 1053–1062.PubMedCrossRefGoogle Scholar
  11. Chamey, P., Treisman, R., Mellon, P., Chao, M., Axel, R., and Maniatis, T., 1984, Differences in human a and ß-globin gene expression in mouse erythroleukemia cells: The role of intragenic sequences, Cell 38: 251–263.CrossRefGoogle Scholar
  12. Chen, C. Y., Howley, P. M., Levinson, A. D., and Seeburg, P. H., 1982, The primary structure and the genetic organization of bovine papilloma virus type 1 genome, Nature 299: 530–535.CrossRefGoogle Scholar
  13. Christman, J. K., Gerber, M., Price, P. M., Flordellis, C., Edelman, J., and Acs, G., 1982, Amplification of expression of hepatitis B surface antigen in 3T3 cells cotransfected with a dominant active gene and cloned viral DNA, Proc. Natl. Acad. Sci. USA 79: 1815–1819.PubMedCrossRefGoogle Scholar
  14. Colbere-Garapin, F., Horodniceanu, F., Kourilsky, P., and Gerapin, A.-C., 1981, A new dominant hybrid selective marker for higher eukaryotic cells, J. Mol. Biol. 150: 1–14.PubMedCrossRefGoogle Scholar
  15. Conrad, S. E., Liu, C.-P., and Botchan, M. R., 1982, Fragment spanning the SV40 replication origin is the only DNA sequence required in cis for viral excision, Science 218: 1223–1225.PubMedCrossRefGoogle Scholar
  16. Crowley, C. W., Liu, C. C., and Levinson, A., 1983, Plasmid-directed synthesis of hepatitis B surface antigen in monkey cells, Mol. Cell. Biol. 3: 44–55.PubMedGoogle Scholar
  17. DiMaio, D., 1984, Eukaryotic cloning vectors based on bovine papillomaviruses, BioEssays 1: 23–26.CrossRefGoogle Scholar
  18. DiMaio, D., Treisman, R. H., and Maniatis, T., 1982, Bovine papilloma virus vector that propagates as a plasmid in both mouse and bacterial cells, Proc. Natl. Acad. Sci. USA 79: 4030–4034.PubMedCrossRefGoogle Scholar
  19. DiMaio, D., Corbin, V., Sibley, E., and Maniatis, T., 1984, High level expression of a cloned HLA heavy chain gene introduced into mouse cells on a bovine papillomavirus vector, Mol. Cell. Biol. 4: 340–350.PubMedGoogle Scholar
  20. Dubois, M. F., Pourcel, C., Rousset, S., Chany, C., and Tiolais, P., 1980, Excretion of hepatitis B surface antigen particles from mouse cells transformed with cloned viral DNA, Proc. Natl. Acad. Sci. USA 77: 4549–4553.PubMedCrossRefGoogle Scholar
  21. Dvoretzky, I., Shober, R., Chattopadhyay, S. K., and Lowy, D. R., 1980, A quantitative in vitro focus forming assay for bovine papilloma virus, Virology 103:369–375.PubMedCrossRefGoogle Scholar
  22. Engel, L. W., Heilman, C. A., and Howley, P. M., 1983, Transcriptional organization of bovine papillomavirus type I, J. Virol. 47:516–528.PubMedGoogle Scholar
  23. Florkiewicz, R. Z., and Rose, J. K., 1984, A cell line expressing vesicular stomatitis virus glycoprotein fuses at low pH, Science 225: 721–723.PubMedCrossRefGoogle Scholar
  24. Florkiewicz, R. Z., Smith, A., Bergmann, J. E., and Rose, J. K., 1983, Isolation of stable mouse cell lines that express cell surface and secreted forms of the vesicular stomatitis virus glycoprotein, J. Cell Biol. 97: 1381–1388.PubMedCrossRefGoogle Scholar
  25. Fukunaga, R., Sokawa, Y., and Nagata, S., 1984, Constitutive production of human inter-ferons by mouse cells with bovine papillomavirus as a vector, Proc. Natl. Acad. Sci. USA 81: 5086–5090.PubMedCrossRefGoogle Scholar
  26. Giri, L, Jouanneau, J., and Yaniv, M., 1983, Comparative studies of the expression of linked Escherichia coli gpt gene and BPV-1 DNAs in transfected cells, Virology 127: 385–396.PubMedCrossRefGoogle Scholar
  27. Gluzman, Y., 1982, Viral Vectors, Cold Spring Harbor laboratory, Cold Spring Harbor, N. Y.Google Scholar
  28. Goodbourn, S., Zinn, K, and Maniatis, T., 1985, Human beta-interferon gene expression is regulated by an inducible enhancer sequence, Cell 41: 509–520.PubMedCrossRefGoogle Scholar
  29. Green, M. R., Treisman, R., and Maniatis, T., 1983, Transcriptional activation of cloned human ß-globin genes by viral immediate-early gene products, Cell 35: 137–148.PubMedCrossRefGoogle Scholar
  30. Groff, D. E., Sundberg, J. P., and Lancaster, W. D., 1983, Extrachromosomal deer fibromavirus DNA in deer fibromas and virus transformed mouse cells, Virology 131: 546–550.PubMedCrossRefGoogle Scholar
  31. Hamada, Y., Tsuijimoto, Y., Ishiura, M., and Susuki, Y., 1983, A vehicle for DNA transfer and for recovery of transferred genes: Charon phage—pBR322 hybrid, Gene 24: 245–253.PubMedCrossRefGoogle Scholar
  32. Hamer, D. H., and Walling, M., 1982, Regulation in vivo of a cloned mammalian gene; cadmium induces the transcription of a mouse metallothionein gene in SV40 vectors, J. Mol. Appl. Genet. 1: 273–288.PubMedGoogle Scholar
  33. Hauser, H., Gross, G., Bruns, W., Hochkeppel, H.-K., Myr, U., and Collins, J., 1982, Induc- ibility of human beta interferon gene in mouse L-cell clones, Nature 296: 650–654.CrossRefGoogle Scholar
  34. Heilman, C. A., Engel, L., Lowy, D. R., and Howley, P. M., 1982, Virus-specific transcription in bovine papillomavirus transformed mouse cells, Virology 119: 22–34.PubMedCrossRefGoogle Scholar
  35. Howard, B. H., Auerbach, J., Widmer, S., and Gottesman, M. E., 1983, X SV2: A plasmid cloning vector that can be stably integrated in E. coli, in: Experimental Manipulation of Gene Expression (M. Inouye, ed.), pp. 137–153, Academic Press, New York.Google Scholar
  36. Howley, P. M., Sarver, N., and Law, M.-F., 1983 Eukaryotic cloning vectors derived from bovine papillomavirus DNA, Methods Enzymol. 101: 387–402.PubMedCrossRefGoogle Scholar
  37. Hsiung, N., Fitts, R., Wilson, S., Milne, A., and Hamer, D., 1984, Efficient production of hepatitis B surface antigen using a bovine papillomavirus—metallothionein vector, J. Mol. Appl. Genet. 2: 497–506.PubMedGoogle Scholar
  38. Imperiale, M. J., Feldman, L. T., and Nevins, J. R., 1983, Activation of gene expression by adenovirus and herpesvirus regulatory genes acting in trans and by a cis-acting adenovirus enhancer element, Cell 35: 127–136.PubMedCrossRefGoogle Scholar
  39. Karin, M., Cathala, G., and Nguyen-Huu, M. C., 1983, Expression and regulation of a human metallothionein gene carried on an autonomously replicating shuttle vector, Proc. Natl. Acad. Sci. USA 80: 4040–4044.PubMedCrossRefGoogle Scholar
  40. Kushner, P. J., Levinson, B. B., and Goodman, H. M., 1982, A plasmid that replicates in both mouse and E. coli cells, J. Mol. Appl. Genet., 1: 527–538.PubMedGoogle Scholar
  41. Lau, Y.-F., and Kan, Y. W., 1983, Versatile cosmid vectors for the isolation, expression, and rescue of gene sequences: Studies with the human a-globin gene cluster, Proc. Natl. Acad. Sci. USA 80: 5225–5229.PubMedCrossRefGoogle Scholar
  42. Law, M.-F., Lowy, D. R., Dvoretzky, I., and Howley, P. M., 1981, Mouse cells transformed by bovine papillomavirus contain only extrachromosomal viral DNA sequences, Proc. Natl. Acad. Sci. USA 78: 2727–2731.PubMedCrossRefGoogle Scholar
  43. Law, M.-F., Howard, B., Sarver, N., and Howley, P. M., 1982, Expression of selective traits in mouse cells transformed with a BPV DNA-derived hybrid molecule containing Escherichia coli gpt, in: Eukaryotic Viral Vectors ( Y. Gluzman, ed.), pp. 79–85, Cold Spring Harbor Press, Cold Spring Harbor, N.Y.Google Scholar
  44. Law, M.-F., Bryne, J. C., and Howley, P. M., 1983, A stable bovine papillomavirus hybrid plasmid that expresses a dominant selective trait, Mol. Cell. Biol. 3: 2110–2115.PubMedGoogle Scholar
  45. Lindenmaier, W., Hauser, H., Greiser de Wilke, I., and Schutz, G., 1982, Gene shuttling: Moving DNA into and out of eucaryotic cells, Nucleic Acids Res. 10: 1243–1256.PubMedCrossRefGoogle Scholar
  46. Liu, C. C., Yansura, D., and Levinson, A. D., 1982, Direct expression of hepatitis B surface antigen in monkey cells from an SV40 vector, DNA 1: 213–221.PubMedCrossRefGoogle Scholar
  47. Lowy, D. R., Dvoretzky, I., Shober, R., Law, M.-F., Engel, L., and Howley, P. M., 1980, In vitro tumorigenic transformation by a defined sub-genomic fragment of bovine papilloma virus DNA, Nature 287: 72–74.Google Scholar
  48. Lund, T., Grosveld, F. G., and Flavell, R. A., 1982, Isolation of transforming DNA by cosmid rescue, Proc. Natl. Acad. Sci. USA 79: 520–524.PubMedCrossRefGoogle Scholar
  49. Lusky, M., and Botchan, M., 1981, Inhibition of SV40 replication in simian cells by specific pBR322 DNA sequences, Nature 293: 79–81.PubMedCrossRefGoogle Scholar
  50. Lusky, M., and Botchan, M., 1984, Characterization of the bovine papillomavirus plasmid maintenance sequences, Cell 36: 391–401.PubMedCrossRefGoogle Scholar
  51. Lusky, M., Berg, L., Weiher, H., and Botchan, M., 1983, Bovine papillomavirus contains an activator of gene expression at the distal end of the early transcription unit, Mol. Cell. Biol. 3: 1108–1122.PubMedGoogle Scholar
  52. Maroteauz, L., Chen, L., Mitrani-Rosenbaum, S., Howley, P. M., and Revel, M., 1983, Cycloheximide induces expression of the human interferon beta 1 gene in mouse cells transformed by bovine papillomavirus—interferon beta 1 recombinants, J. Virol. 47: 89–95.Google Scholar
  53. Matthias, P. D., Bernard, H. U., Scott, A., Brady, G., Hashimoto-Gotoh, T., and Schutz, G., 1983, A bovine papillomavirus vector with a dominant resistance marker replicates extrachromosomally in mouse and E. coli cells, EMBO J. 2: 1487–1492.PubMedGoogle Scholar
  54. Meneguzzi, G., Binetruy, B., Grisoni, M., and Cuzin, F., 1984, Plasmidial maintenance in rodent fibroblasts of a BPV-1—pBR322 shuttle vector without immediately apparent oncogenic transformation of the recipient cells, EMBO J. 3: 365–371.PubMedGoogle Scholar
  55. Mitrani-Rosenbaum, S., Maroteaux, L., Mory, Y., Revel, M., and Howley, P. M., 1983, Inducible expression of the human interferon beta 1 gene linked to a bovine papillomavirus DNA vector and maintained extrachromosomally in mouse cells, Mol. Cell. Biol. 3: 233.PubMedGoogle Scholar
  56. Moar, M. H., Campo, M. S., Laird, H., and Jarrett, W. F. H., 1981, Persistence of nonintegrated viral DNA in bovine cells transformed by bovine papillomavirus type 2, Nature 293: 749–751.PubMedCrossRefGoogle Scholar
  57. Morgan, D. M., and Meinke, W., 1980, Isolation of clones of hamster embryo cells transformed by the bovine papillomavirus, Curr. Microbiol. 3: 247–251.CrossRefGoogle Scholar
  58. Moriarty, A. M., Hoyer, B. H., Shih, J. W., Gerin, J. L., and Hamer, D. H., 1981, Expression of the hepatitis B virus surface antigen gene in cell culture using a SV40 vector, Proc. Natl. Acad. Sci. USA 78: 2606–2610.PubMedCrossRefGoogle Scholar
  59. Ohno, S., and Taniguchi, T., 1982, Inducer-responsive expression of the cloned human beta, interferon gene introduced into cultured mouse cells, Nucleic Acids Res. 10: 967–977.PubMedCrossRefGoogle Scholar
  60. Ostrawski, M. C., Richard-Foy, H., Wollord, R. G., Berand, D. S., and Hager, G., 1983, Glucocorticoid regulation of transcription at an amplified episomal promoter, Mol. Cell. Biol. 3: 2045–2057.Google Scholar
  61. Pavlakis, G. N., and Hamer, D. H., 1983a, Regulation of a metallothionein—growth hormone hybrid gene in bovine papilloma virus, Proc. Natl. Acad. Sci. USA 80: 397–401.PubMedCrossRefGoogle Scholar
  62. Pavlakis, G. N., and Hamer, D. H., 1983b, Expression of cloned growth hormone and me- tallothionein genes in heterologous cells, Recent Prog. Horm. Res. 39: 353–385.PubMedGoogle Scholar
  63. Perucho, M., Hanahan, D., and Wigler, M., 1980, Genetic and physical linkage of exogenous DNA sequences in transformed cells, Cell 22: 309–317.PubMedCrossRefGoogle Scholar
  64. Pintel, D., Merchlinsky, M. J., and Ward, D. C., 1984, Expression of minute virus of mice (MVM) structural proteins in murine cell lines transformed by bovine papilloma—MVM plasmid chimeras, J. Virol. 52: 320–327.PubMedGoogle Scholar
  65. Pitha, P. M., Ciufo, D. M., Kellum, M., Raj, N. B. K., Reyes, G. R., and Hayward, G. S., 1982, Induction of human beta interferon synthesis with poly (rI-rC) in mouse cells transfected with cloned cDNA plasmids, Proc. Natl. Acad. Sci. USA 79: 4337–4341.PubMedCrossRefGoogle Scholar
  66. Ramabhadran, T. V., Reitz, B. A., and Tiemeier, D. C., 1984, Synthesis and glycosylation of the common a subunit of human glycoprotein hormones in mouse cells, Proc. Natl. Acad. Sci. USA 81: 6701–6705.PubMedCrossRefGoogle Scholar
  67. Ramabhadran, T. V., Reitz, B. A., and Shah, D. M., 1985, Isolation and high level expression of the bovine growth hormone gene in heterologous mammalian cells, Gene 38: 111–125.PubMedCrossRefGoogle Scholar
  68. Richards, R. I., Heguy, A., and Karin, M., 1984, Structural and functional analysis of the human metallothionein-IA gene: Differential induction by metal ions and glucocorticoids, Cell 37: 263–272.PubMedCrossRefGoogle Scholar
  69. Ringold, G. M., 1983, Regulation of mouse mammary tumor virus gene expression by glucocorticoid hormones, Curr. Top. Microbiol. pp. 79–103.Google Scholar
  70. Rösl, R., Waldeck, W., and Sauer, G., 1983, Isolation of episomal bovine papillomavirus chromatin and identification of a DNase I-hypersensitive region, J. Virol. 46: 567–574.PubMedGoogle Scholar
  71. Sambrook, J., Rogers, L., White, J., and Gething, M. J., 1985, Lines of BPV-transformed murine cells that constitutively express influenza virus hemagglutinin, EMBO I. 4: 91–103.Google Scholar
  72. Sarver, N., Gruss, P., Law, M.-F., Khoury, G., and Howley, P. M., 1981, Bovine papilloma virus deoxyribonucleic acid: A novel eucaryotic cloning vector, Mol. Cell. Biol. 1: 486–496.PubMedGoogle Scholar
  73. Sarver, N., Byrne, J. C., and Howley, P. M., 1982, Transformation and replication in mouse cells of a bovine papillomavirus—pML2 plasmid vector that can be rescued in bacteria, Proc. Natl. Acad. Sci. USA 79: 7147–7151.PubMedCrossRefGoogle Scholar
  74. Sarver, N., Mitrani-Rosenbaum, S., Law, M.-F., McAllister, W. T., Bryne, J. C., and Howley, P. M., 1983, Bovine papillomavirus shuttle vectors, in: Gene Expression ( J. Setlow and A. Hollaender, eds.), pp. 173–190, Plenum Press, New York.Google Scholar
  75. Schaffner, W., 1980, Direct transfer of cloned genes from bacteria to mammalian cells, Proc. Natl. Acad. Sci. USA 77: 2163–2167.PubMedCrossRefGoogle Scholar
  76. Schenborn, E. T., Lund, E., Mitchen, J. L., and Dahlberg, J. E., 1985, Expression of a human Ul RNA gene introduced into mouse cells via bovine papilloma virus DNA vectors, Mol. Cell. Biol. 5: 1318–1326.PubMedGoogle Scholar
  77. Sekiguchi, Y., Nishimoto, T., Kai, R., and Sekiguchi, M., 1983, Recovery of a hybrid vector, derived from bovine papillomavirus DNA, pBR322 and the HSV tk gene, by bacterial transformation with extrachromosomal DNA from transfected rodent cells, Gene 21: 267–272.PubMedCrossRefGoogle Scholar
  78. Siddiqui, A., 1983, Expression of hepatitis B virus surface antigen gene in cultured cells by using recombinant plasmid vectors, Mol. Cell. Biol. 3: 143–146.PubMedGoogle Scholar
  79. Southern, P. J., and Berg, P., 1982, Transformation of mammalian cells to antibiotic resistance with a bacterial gene under control of the SV40 early region promoter, J. Mol. Appl. Genet. 1: 327–341.PubMedGoogle Scholar
  80. Stenlund, A., Lamy, D., Moreno-Lopez, J., Ahola, H., Pettersson, U., and Tiollais, P., 1983a, Secretion of the hepatitis B virus surface antigen from mouse cells using an extra-chromosomal eucaryotic vector, EMBO J. 2: 669–673.PubMedGoogle Scholar
  81. Stenlund, A., Moreno-Lopez, J., Ahola, H., and Pettersson, U., 1983b, European elk papillomavirus: Characterization of the genome, induction of tumors in animals and transformation in vitro, J. Virol. 48: 370–376.PubMedGoogle Scholar
  82. Stratowa, C., Doehmer, J., Wang, Y., and Hofschneider, P. H., 1982, Recombinant retroviral DNA yielding high expression of hepatitis B surface antigen, EMBO I. 1: 1573–1578.Google Scholar
  83. Treisman, R., Orkin, S. H., and Maniatis, T., 1983, Specific transcription and RNA splicing defects in five cloned beta thalassaemia genes, Nature 302: 591–596.PubMedCrossRefGoogle Scholar
  84. Turek, L. P., Byrne, J. C., Lowy, D. R., Dvoretzky, I., Friedman, R. M., and Howley, P. M., 1982, Interferon induces morphologic reversion with elimination of extrachromosomal viral genomes in bovine papillomavirus-transformed mouse cells, Proc. Natl. Acad. Sci. USA 79: 7914–7918.PubMedCrossRefGoogle Scholar
  85. Wang, Y., Stratowa, C., Schaefer-Ridder, M., Doehmer, J., and Hofschneider, P. H., 1983, Enhanced production of hepatitis B surface antigen in NIH3T3 mouse fibroblasts by using extrachromosomally replicating bovine papillomavirus vector, Mol. Cell. Biol. 3: 1032–1039.PubMedGoogle Scholar
  86. Watts, S. L., Ostrow, R. S., Phelps, W. C., Prince, J. T., and Faras, A. J., 1983, Free cottontail rabbit papillomavirus DNA persists in warts and carcinomas of infected rabbits and in cells in culture transformed with virus or viral DNA, Virology 125: 127–138.PubMedCrossRefGoogle Scholar
  87. Watts, S. L., Phelps, W. C., Ostrow, R. S., Zachow, K. R., and Faras, A. J., 1984, Cellular transformation by human papillomavirus DNA in vitro, Science 225: 634–636.PubMedCrossRefGoogle Scholar
  88. Zinn, K., Mellon, P., Ptashne, M., and Maniatis, T., 1982, Regulated expression of an extrachromosomal human beta interferon gene in mouse cells, Proc. Natl. Acad. Sci. USA 79: 4897–4901.PubMedCrossRefGoogle Scholar
  89. Zinn, K., DiMaio, D., and Maniatis, T., 1983, Identification of two distinct regulatory regions adjacent to the human 13 interferon gene, Cell 34: 865–879.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • Daniel DiMaio
    • 1
  1. 1.Department of Human GeneticsYale University School of MedicineNew HavenUSA

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