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. 1994 Dec;68(12):8365–8373. doi: 10.1128/jvi.68.12.8365-8373.1994

The genomes of the animal papillomaviruses European elk papillomavirus, deer papillomavirus, and reindeer papillomavirus contain a novel transforming gene (E9) near the early polyadenylation site.

A Eriksson 1, A C Stewart 1, J Moreno-Lopéz 1, U Pettersson 1
PMCID: PMC237305  PMID: 7966628

Abstract

We report that the genomes of reindeer papillomavirus (RPV), European elk papillomavirus (EEPV), and deer papillomavirus (DPV) contain a short conserved translational open reading frame (ORF), E9, which is located between the E5 ORF and the early polyadenylation site. In RPV, DPV, and EEPV, E9 ORFs have the potential to encode extremely hydrophobic polypeptides of approximately 40 amino acids. In mouse C127 cells transformed by EEPV and RPV, there exists a unique, abundant mRNA species of approximately 700 nucleotides which has the capacity to encode an E9 polypeptide. This mRNA is transcribed from a previously unrecognized promoter at position 4030 in the EEPV genome. The EEPV E9 ORF exhibits weak transforming activity in C127 cells and primary rat embryo fibroblasts. We also show that EEPV E5 is the major oncogene in the EEPV genome when assayed in C127 cells, although it is less efficient in transformation than the E5 genes of bovine papillomavirus type 1, DPV, and RPV.

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Selected References

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  1. Ahola H., Bergman P., Ström A. C., Moreno-Lopéz J., Pettersson U. Organization and expression of the transforming region from the European elk papillomavirus (EEPV). Gene. 1986;50(1-3):195–205. doi: 10.1016/0378-1119(86)90324-0. [DOI] [PubMed] [Google Scholar]
  2. Ahola H., Stenlund A., Moreno-Lopez J., Pettersson U. Sequences of bovine papillomavirus type 1 DNA--functional and evolutionary implications. Nucleic Acids Res. 1983 May 11;11(9):2639–2650. doi: 10.1093/nar/11.9.2639. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Ahola H., Stenlund A., Moreno-López J., Pettersson U. Promoters and processing sites within the transforming region of bovine papillomavirus type 1. J Virol. 1987 Jul;61(7):2240–2244. doi: 10.1128/jvi.61.7.2240-2244.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Baker C. C., Howley P. M. Differential promoter utilization by the bovine papillomavirus in transformed cells and productively infected wart tissues. EMBO J. 1987 Apr;6(4):1027–1035. doi: 10.1002/j.1460-2075.1987.tb04855.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bergman P., Ustav M., Sedman J., Moreno-Lopéz J., Vennström B., Pettersson U. The E5 gene of bovine papillomavirus type 1 is sufficient for complete oncogenic transformation of mouse fibroblasts. Oncogene. 1988 May;2(5):453–459. [PubMed] [Google Scholar]
  6. Burkhardt A., DiMaio D., Schlegel R. Genetic and biochemical definition of the bovine papillomavirus E5 transforming protein. EMBO J. 1987 Aug;6(8):2381–2385. doi: 10.1002/j.1460-2075.1987.tb02515.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Burkhardt A., Willingham M., Gay C., Jeang K. T., Schlegel R. The E5 oncoprotein of bovine papillomavirus is oriented asymmetrically in Golgi and plasma membranes. Virology. 1989 May;170(1):334–339. doi: 10.1016/0042-6822(89)90391-7. [DOI] [PubMed] [Google Scholar]
  8. Chan S. Y., Bernard H. U., Ong C. K., Chan S. P., Hofmann B., Delius H. Phylogenetic analysis of 48 papillomavirus types and 28 subtypes and variants: a showcase for the molecular evolution of DNA viruses. J Virol. 1992 Oct;66(10):5714–5725. doi: 10.1128/jvi.66.10.5714-5725.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Chen E. Y., Howley P. M., Levinson A. D., Seeburg P. H. The primary structure and genetic organization of the bovine papillomavirus type 1 genome. Nature. 1982 Oct 7;299(5883):529–534. doi: 10.1038/299529a0. [DOI] [PubMed] [Google Scholar]
  10. DiMaio D., Guralski D., Schiller J. T. Translation of open reading frame E5 of bovine papillomavirus is required for its transforming activity. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1797–1801. doi: 10.1073/pnas.83.6.1797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dvoretzky I., Shober R., Chattopadhyay S. K., Lowy D. R. A quantitative in vitro focus assay for bovine papilloma virus. Virology. 1980 Jun;103(2):369–375. doi: 10.1016/0042-6822(80)90195-6. [DOI] [PubMed] [Google Scholar]
  12. Eriksson A., Ahola H., Pettersson U., Moreno-Lopez J. Genome of the European elk papillomavirus (EEPV). Virus Genes. 1988 Mar;1(2):123–133. doi: 10.1007/BF00555932. [DOI] [PubMed] [Google Scholar]
  13. Favaloro J., Treisman R., Kamen R. Transcription maps of polyoma virus-specific RNA: analysis by two-dimensional nuclease S1 gel mapping. Methods Enzymol. 1980;65(1):718–749. doi: 10.1016/s0076-6879(80)65070-8. [DOI] [PubMed] [Google Scholar]
  14. Goldstein D. J., Andresson T., Sparkowski J. J., Schlegel R. The BPV-1 E5 protein, the 16 kDa membrane pore-forming protein and the PDGF receptor exist in a complex that is dependent on hydrophobic transmembrane interactions. EMBO J. 1992 Dec;11(13):4851–4859. doi: 10.1002/j.1460-2075.1992.tb05591.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Goldstein D. J., Kulke R., Dimaio D., Schlegel R. A glutamine residue in the membrane-associating domain of the bovine papillomavirus type 1 E5 oncoprotein mediates its binding to a transmembrane component of the vacuolar H(+)-ATPase. J Virol. 1992 Jan;66(1):405–413. doi: 10.1128/jvi.66.1.405-413.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Goldstein D. J., Schlegel R. The E5 oncoprotein of bovine papillomavirus binds to a 16 kd cellular protein. EMBO J. 1990 Jan;9(1):137–145. doi: 10.1002/j.1460-2075.1990.tb08089.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. Groff D. E., Lancaster W. D. Genetic analysis of the 3' early region transformation and replication functions of bovine papillomavirus type 1. Virology. 1986 Apr 15;150(1):221–230. doi: 10.1016/0042-6822(86)90281-3. [DOI] [PubMed] [Google Scholar]
  19. Groff D. E., Lancaster W. D. Molecular cloning and nucleotide sequence of deer papillomavirus. J Virol. 1985 Oct;56(1):85–91. doi: 10.1128/jvi.56.1.85-91.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Groff D. E., Sundberg J. P., Lancaster W. D. Extrachromosomal deer fibromavirus DNA in deer fibromas and virus-transformed mouse cells. Virology. 1983 Dec;131(2):546–550. doi: 10.1016/0042-6822(83)90519-6. [DOI] [PubMed] [Google Scholar]
  21. Haugen T. H., Turek L. P., Mercurio F. M., Cripe T. P., Olson B. J., Anderson R. D., Seidl D., Karin M., Schiller J. Sequence-specific and general transcriptional activation by the bovine papillomavirus-1 E2 trans-activator require an N-terminal amphipathic helix-containing E2 domain. EMBO J. 1988 Dec 20;7(13):4245–4253. doi: 10.1002/j.1460-2075.1988.tb03322.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Horwitz B. H., Burkhardt A. L., Schlegel R., DiMaio D. 44-amino-acid E5 transforming protein of bovine papillomavirus requires a hydrophobic core and specific carboxyl-terminal amino acids. Mol Cell Biol. 1988 Oct;8(10):4071–4078. doi: 10.1128/mcb.8.10.4071. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Horwitz B. H., Weinstat D. L., DiMaio D. Transforming activity of a 16-amino-acid segment of the bovine papillomavirus E5 protein linked to random sequences of hydrophobic amino acids. J Virol. 1989 Nov;63(11):4515–4519. doi: 10.1128/jvi.63.11.4515-4519.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Jackson M. E., Pennie W. D., McCaffery R. E., Smith K. T., Grindlay G. J., Campo M. S. The B subgroup bovine papillomaviruses lack an identifiable E6 open reading frame. Mol Carcinog. 1991;4(5):382–387. doi: 10.1002/mc.2940040510. [DOI] [PubMed] [Google Scholar]
  25. Kulke R., DiMaio D. Biological properties of the deer papillomavirus E5 gene in mouse C127 cells: growth transformation, induction of DNA synthesis, and activation of the platelet-derived growth factor receptor. J Virol. 1991 Sep;65(9):4943–4949. doi: 10.1128/jvi.65.9.4943-4949.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Kulke R., Horwitz B. H., Zibello T., DiMaio D. The central hydrophobic domain of the bovine papillomavirus E5 transforming protein can be functionally replaced by many hydrophobic amino acid sequences containing a glutamine. J Virol. 1992 Jan;66(1):505–511. doi: 10.1128/jvi.66.1.505-511.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Kyte J., Doolittle R. F. A simple method for displaying the hydropathic character of a protein. J Mol Biol. 1982 May 5;157(1):105–132. doi: 10.1016/0022-2836(82)90515-0. [DOI] [PubMed] [Google Scholar]
  28. Law M. F., Lowy D. R., Dvoretzky I., Howley P. M. Mouse cells transformed by bovine papillomavirus contain only extrachromosomal viral DNA sequences. Proc Natl Acad Sci U S A. 1981 May;78(5):2727–2731. doi: 10.1073/pnas.78.5.2727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Martin P., Vass W. C., Schiller J. T., Lowy D. R., Velu T. J. The bovine papillomavirus E5 transforming protein can stimulate the transforming activity of EGF and CSF-1 receptors. Cell. 1989 Oct 6;59(1):21–32. doi: 10.1016/0092-8674(89)90866-0. [DOI] [PubMed] [Google Scholar]
  30. Maxam A. M., Gilbert W. A new method for sequencing DNA. Proc Natl Acad Sci U S A. 1977 Feb;74(2):560–564. doi: 10.1073/pnas.74.2.560. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Moreno-Lopez J., Ahola H., Eriksson A., Bergman P., Pettersson U. Reindeer papillomavirus transforming properties correlate with a highly conserved E5 region. J Virol. 1987 Nov;61(11):3394–3400. doi: 10.1128/jvi.61.11.3394-3400.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. O'Banion M. K., Winn V. D., Settleman J., Young D. A. Genetic definition of a new bovine papillomavirus type 1 open reading frame, E5B, that encodes a hydrophobic protein involved in altering host-cell protein processing. J Virol. 1993 Jun;67(6):3427–3434. doi: 10.1128/jvi.67.6.3427-3434.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. O'Banion M. K., Young D. A. Bovine papillomavirus type 1 alters the processing of host glucose- and calcium-modulated endoplasmic reticulum proteins. J Virol. 1991 Jul;65(7):3481–3488. doi: 10.1128/jvi.65.7.3481-3488.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Pennie W. D., Grindlay G. J., Cairney M., Campo M. S. Analysis of the transforming functions of bovine papillomavirus type 4. Virology. 1993 Apr;193(2):614–620. doi: 10.1006/viro.1993.1169. [DOI] [PubMed] [Google Scholar]
  35. Petti L., DiMaio D. Stable association between the bovine papillomavirus E5 transforming protein and activated platelet-derived growth factor receptor in transformed mouse cells. Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6736–6740. doi: 10.1073/pnas.89.15.6736. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Petti L., Nilson L. A., DiMaio D. Activation of the platelet-derived growth factor receptor by the bovine papillomavirus E5 transforming protein. EMBO J. 1991 Apr;10(4):845–855. doi: 10.1002/j.1460-2075.1991.tb08017.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Pfister H. Biology and biochemistry of papillomaviruses. Rev Physiol Biochem Pharmacol. 1984;99:111–181. doi: 10.1007/BFb0027716. [DOI] [PubMed] [Google Scholar]
  38. Schiller J. T., Vass W. C., Lowy D. R. Identification of a second transforming region in bovine papillomavirus DNA. Proc Natl Acad Sci U S A. 1984 Dec;81(24):7880–7884. doi: 10.1073/pnas.81.24.7880. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Schiller J. T., Vass W. C., Vousden K. H., Lowy D. R. E5 open reading frame of bovine papillomavirus type 1 encodes a transforming gene. J Virol. 1986 Jan;57(1):1–6. doi: 10.1128/jvi.57.1.1-6.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Schlegel R., Wade-Glass M., Rabson M. S., Yang Y. C. The E5 transforming gene of bovine papillomavirus encodes a small, hydrophobic polypeptide. Science. 1986 Jul 25;233(4762):464–467. doi: 10.1126/science.3014660. [DOI] [PubMed] [Google Scholar]
  41. Stenlund A., Moreno-Lopez J., Ahola H., Pettersson U. European elk papillomavirus: characterization of the genome, induction of tumors in animals, and transformation in vitro. J Virol. 1983 Nov;48(2):370–376. doi: 10.1128/jvi.48.2.370-376.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Yang Y. C., Okayama H., Howley P. M. Bovine papillomavirus contains multiple transforming genes. Proc Natl Acad Sci U S A. 1985 Feb;82(4):1030–1034. doi: 10.1073/pnas.82.4.1030. [DOI] [PMC free article] [PubMed] [Google Scholar]

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