Skip to main content
Journal of Virology logoLink to Journal of Virology
. 1987 Aug;61(8):2599–2606. doi: 10.1128/jvi.61.8.2599-2606.1987

Enhancers and trans-acting E2 transcriptional factors of papillomaviruses.

H Hirochika, T R Broker, L T Chow
PMCID: PMC255708  PMID: 3037119

Abstract

The upstream regulatory regions of human papillomavirus (HPV) types 1, 6b, 7, 11, 16, and 18, bovine papillomavirus type 1, and cottontail rabbit papillomavirus were cloned into transcriptional enhancer assay plasmids which carry the simian virus 40 early promoter lacking its own enhancer and the bacterial gene encoding chloramphenicol acetyltransferase (EC 2.3.1.28) (CAT). Enhancer activity, reflected by CAT gene expression, was detected in all of the upstream regulatory regions tested only when the recombinants were cotransfected with plasmids which express an intact E2 open reading frame of HPV types 1 and 11 or bovine papillomavirus type 1. Each E2 protein stimulated the enhancer from the same virus and, to somewhat lesser degrees, also those from the heterologous viruses. Hence, the enhancer and the E2 protein are functionally conserved among papillomaviruses. There was some nonreciprocity in the extent of trans-activation in heterologous E2-enhancer interactions. Primer extension analyses demonstrated that the E2 proteins increased the abundance of CAT gene mRNA. Tandem multiplication of the HPV type 11 enhancer sequence dramatically increased its response to E2 stimulation; this is possibly relevant to the pathogenicity of papillomaviruses.

Full text

PDF
2599

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson C. W., Lewis J. B., Atkins J. F., Gesteland R. F. Cell-free synthesis of adenovirus 2 proteins programmed by fractionated messenger RNA: a comparison of polypeptide products and messenger RNA lengths. Proc Natl Acad Sci U S A. 1974 Jul;71(7):2756–2760. doi: 10.1073/pnas.71.7.2756. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Androphy E. J., Lowy D. R., Schiller J. T. Bovine papillomavirus E2 trans-activating gene product binds to specific sites in papillomavirus DNA. Nature. 1987 Jan 1;325(6099):70–73. doi: 10.1038/325070a0. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Boshart M., zur Hausen H. Human papillomaviruses in Buschke-Löwenstein tumors: physical state of the DNA and identification of a tandem duplication in the noncoding region of a human papillomavirus 6 subtype. J Virol. 1986 Jun;58(3):963–966. doi: 10.1128/jvi.58.3.963-966.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Broker T. R. Structure and genetic expression of papillomaviruses. Obstet Gynecol Clin North Am. 1987 Jun;14(2):329–348. [PubMed] [Google Scholar]
  6. Chow L. T., Nasseri M., Wolinsky S. M., Broker T. R. Human papillomavirus types 6 and 11 mRNAs from genital condylomata acuminata. J Virol. 1987 Aug;61(8):2581–2588. doi: 10.1128/jvi.61.8.2581-2588.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chow L. T., Reilly S. S., Broker T. R., Taichman L. B. Identification and mapping of human papillomavirus type 1 RNA transcripts recovered from plantar warts and infected epithelial cell cultures. J Virol. 1987 Jun;61(6):1913–1918. doi: 10.1128/jvi.61.6.1913-1918.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Church G. M., Ephrussi A., Gilbert W., Tonegawa S. Cell-type-specific contacts to immunoglobulin enhancers in nuclei. 1985 Feb 28-Mar 6Nature. 313(6005):798–801. doi: 10.1038/313798a0. [DOI] [PubMed] [Google Scholar]
  9. Cole S. T., Danos O. Nucleotide sequence and comparative analysis of the human papillomavirus type 18 genome. Phylogeny of papillomaviruses and repeated structure of the E6 and E7 gene products. J Mol Biol. 1987 Feb 20;193(4):599–608. doi: 10.1016/0022-2836(87)90343-3. [DOI] [PubMed] [Google Scholar]
  10. Cole S. T., Streeck R. E. Genome organization and nucleotide sequence of human papillomavirus type 33, which is associated with cervical cancer. J Virol. 1986 Jun;58(3):991–995. doi: 10.1128/jvi.58.3.991-995.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Danos O., Engel L. W., Chen E. Y., Yaniv M., Howley P. M. Comparative analysis of the human type 1a and bovine type 1 papillomavirus genomes. J Virol. 1983 May;46(2):557–566. doi: 10.1128/jvi.46.2.557-566.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Danos O., Georges E., Orth G., Yaniv M. Fine structure of the cottontail rabbit papillomavirus mRNAs expressed in the transplantable VX2 carcinoma. J Virol. 1985 Mar;53(3):735–741. doi: 10.1128/jvi.53.3.735-741.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Dartmann K., Schwarz E., Gissmann L., zur Hausen H. The nucleotide sequence and genome organization of human papilloma virus type 11. Virology. 1986 May;151(1):124–130. doi: 10.1016/0042-6822(86)90110-8. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Ephrussi A., Church G. M., Tonegawa S., Gilbert W. B lineage--specific interactions of an immunoglobulin enhancer with cellular factors in vivo. Science. 1985 Jan 11;227(4683):134–140. doi: 10.1126/science.3917574. [DOI] [PubMed] [Google Scholar]
  16. Ghosh P. K., Lebowitz P. Simian virus 40 early mRNA's contain multiple 5' termini upstream and downstream from a Hogness-Goldberg sequence; a shift in 5' termini during the lytic cycle is mediated by large T antigen. J Virol. 1981 Oct;40(1):224–240. doi: 10.1128/jvi.40.1.224-240.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Gorman C. M., Howard B. H., Reeves R. Expression of recombinant plasmids in mammalian cells is enhanced by sodium butyrate. Nucleic Acids Res. 1983 Nov 11;11(21):7631–7648. doi: 10.1093/nar/11.21.7631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Gorman C. M., Merlino G. T., Willingham M. C., Pastan I., Howard B. H. The Rous sarcoma virus long terminal repeat is a strong promoter when introduced into a variety of eukaryotic cells by DNA-mediated transfection. Proc Natl Acad Sci U S A. 1982 Nov;79(22):6777–6781. doi: 10.1073/pnas.79.22.6777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Gorman C. M., Rigby P. W., Lane D. P. Negative regulation of viral enhancers in undifferentiated embryonic stem cells. Cell. 1985 Sep;42(2):519–526. doi: 10.1016/0092-8674(85)90109-6. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Hanahan D. Studies on transformation of Escherichia coli with plasmids. J Mol Biol. 1983 Jun 5;166(4):557–580. doi: 10.1016/s0022-2836(83)80284-8. [DOI] [PubMed] [Google Scholar]
  23. Herr W., Clarke J. The SV40 enhancer is composed of multiple functional elements that can compensate for one another. Cell. 1986 May 9;45(3):461–470. doi: 10.1016/0092-8674(86)90332-6. [DOI] [PubMed] [Google Scholar]
  24. Herrera-Estrella L., Van den Broeck G., Maenhaut R., Van Montagu M., Schell J., Timko M., Cashmore A. Light-inducible and chloroplast-associated expression of a chimaeric gene introduced into Nicotiana tabacum using a Ti plasmid vector. Nature. 1984 Jul 12;310(5973):115–120. doi: 10.1038/310115a0. [DOI] [PubMed] [Google Scholar]
  25. Kadesch T., Berg P. Effects of the position of the simian virus 40 enhancer on expression of multiple transcription units in a single plasmid. Mol Cell Biol. 1986 Jul;6(7):2593–2601. doi: 10.1128/mcb.6.7.2593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Laimins L. A., Khoury G., Gorman C., Howard B., Gruss P. Host-specific activation of transcription by tandem repeats from simian virus 40 and Moloney murine sarcoma virus. Proc Natl Acad Sci U S A. 1982 Nov;79(21):6453–6457. doi: 10.1073/pnas.79.21.6453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Lusky M., Berg L., Weiher H., Botchan M. Bovine papilloma virus contains an activator of gene expression at the distal end of the early transcription unit. Mol Cell Biol. 1983 Jun;3(6):1108–1122. doi: 10.1128/mcb.3.6.1108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Lusky M., Botchan M. R. Characterization of the bovine papilloma virus plasmid maintenance sequences. Cell. 1984 Feb;36(2):391–401. doi: 10.1016/0092-8674(84)90232-0. [DOI] [PubMed] [Google Scholar]
  29. Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
  30. Messing J. New M13 vectors for cloning. Methods Enzymol. 1983;101:20–78. doi: 10.1016/0076-6879(83)01005-8. [DOI] [PubMed] [Google Scholar]
  31. Moskaluk C., Bastia D. The E2 "gene" of bovine papillomavirus encodes an enhancer-binding protein. Proc Natl Acad Sci U S A. 1987 Mar;84(5):1215–1218. doi: 10.1073/pnas.84.5.1215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Nasseri M., Wettstein F. O. Cottontail rabbit papillomavirus-specific transcripts in transplantable tumors with integrated DNA. Virology. 1984 Oct 30;138(2):362–367. doi: 10.1016/0042-6822(84)90362-3. [DOI] [PubMed] [Google Scholar]
  33. Paskalis H., Felber B. K., Pavlakis G. N. Cis-acting sequences responsible for the transcriptional activation of human T-cell leukemia virus type I constitute a conditional enhancer. Proc Natl Acad Sci U S A. 1986 Sep;83(17):6558–6562. doi: 10.1073/pnas.83.17.6558. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Pfister H., Krubke J., Dietrich W., Iftner T., Fuchs P. G. Classification of the papillomaviruses--mapping the genome. Ciba Found Symp. 1986;120:3–22. doi: 10.1002/9780470513309.ch2. [DOI] [PubMed] [Google Scholar]
  35. Phelps W. C., Howley P. M. Transcriptional trans-activation by the human papillomavirus type 16 E2 gene product. J Virol. 1987 May;61(5):1630–1638. doi: 10.1128/jvi.61.5.1630-1638.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Rando R. F., Lancaster W. D., Han P., Lopez C. The noncoding region of HPV-6vc contains two distinct transcriptional enhancing elements. Virology. 1986 Dec;155(2):545–556. doi: 10.1016/0042-6822(86)90215-1. [DOI] [PubMed] [Google Scholar]
  37. Rosen C. A., Sodroski J. G., Kettman R., Haseltine W. A. Activation of enhancer sequences in type II human T-cell leukemia virus and bovine leukemia virus long terminal repeats by virus-associated trans-acting regulatory factors. J Virol. 1986 Mar;57(3):738–744. doi: 10.1128/jvi.57.3.738-744.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Sarver N., Muschel R., Byrne J. C., Khoury G., Howley P. M. Enhancer-dependent expression of the rat preproinsulin gene in bovine papillomavirus type 1 vectors. Mol Cell Biol. 1985 Dec;5(12):3507–3516. doi: 10.1128/mcb.5.12.3507. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Schirm S., Jiricny J., Schaffner W. The SV40 enhancer can be dissected into multiple segments, each with a different cell type specificity. Genes Dev. 1987 Mar;1(1):65–74. doi: 10.1101/gad.1.1.65. [DOI] [PubMed] [Google Scholar]
  41. Schneider-Gädicke A., Schwarz E. Different human cervical carcinoma cell lines show similar transcription patterns of human papillomavirus type 18 early genes. EMBO J. 1986 Sep;5(9):2285–2292. doi: 10.1002/j.1460-2075.1986.tb04496.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Sen R., Baltimore D. Multiple nuclear factors interact with the immunoglobulin enhancer sequences. Cell. 1986 Aug 29;46(5):705–716. doi: 10.1016/0092-8674(86)90346-6. [DOI] [PubMed] [Google Scholar]
  43. Smotkin D., Wettstein F. O. Transcription of human papillomavirus type 16 early genes in a cervical cancer and a cancer-derived cell line and identification of the E7 protein. Proc Natl Acad Sci U S A. 1986 Jul;83(13):4680–4684. doi: 10.1073/pnas.83.13.4680. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Spalholz B. A., Yang Y. C., Howley P. M. Transactivation of a bovine papilloma virus transcriptional regulatory element by the E2 gene product. Cell. 1985 Aug;42(1):183–191. doi: 10.1016/s0092-8674(85)80114-8. [DOI] [PubMed] [Google Scholar]
  45. Stenlund A., Zabielski J., Ahola H., Moreno-Lopez J., Pettersson U. Messenger RNAs from the transforming region of bovine papilloma virus type I. J Mol Biol. 1985 Apr 20;182(4):541–554. doi: 10.1016/0022-2836(85)90240-2. [DOI] [PubMed] [Google Scholar]
  46. Waldeck W., Rösl F., Zentgraf H. Origin of replication in episomal bovine papilloma virus type 1 DNA isolated from transformed cells. EMBO J. 1984 Sep;3(9):2173–2178. doi: 10.1002/j.1460-2075.1984.tb02109.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Wasylyk B., Wasylyk C., Augereau P., Chambon P. The SV40 72 bp repeat preferentially potentiates transcription starting from proximal natural or substitute promoter elements. Cell. 1983 Feb;32(2):503–514. doi: 10.1016/0092-8674(83)90470-1. [DOI] [PubMed] [Google Scholar]
  48. 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]
  49. Zenke M., Grundström T., Matthes H., Wintzerith M., Schatz C., Wildeman A., Chambon P. Multiple sequence motifs are involved in SV40 enhancer function. EMBO J. 1986 Feb;5(2):387–397. doi: 10.1002/j.1460-2075.1986.tb04224.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. zur Hausen H., Gissmann L., Schlehofer J. R. Viruses in the etiology of human genital cancer. Prog Med Virol. 1984;30:170–186. [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES