1887

Journal of General Virology header logo

Volume 77, Issue 9

Promoter Activity of Sequences Located Upstream of the Human Papillomavirus Types 16 and 18 Late Regions Free

Abstract

The regulation of human papillomavirus (HPV) late gene expression is difficult to analyse because the late proteins L1 and L2 are only produced in the upper layers of terminally differentiated keratinocytes. However, for the minor capsid protein L2 of HPV types 1, 6, 11 and 16, rare mRNAs or cDNAs starting 3′ of the E5 open reading frame (ORF) were previously described. In order to analyse whether the DNA region preceding the late ORFs (late upstream region, LUR) of HPV-16 and HPV-18 has promoter activity, transient transfection assays employing luciferase reporter constructs were performed. The results show that the LUR of HPV-16 and HPV-18 exhibits an orientation-dependent promoter activity in different cells. By analysing 3′-deletion mutants of the HPV-16 LUR, we identified 78 bp within the sequence between the E5 and L2 ORFs to be critical for the promoter activity. Furthermore, the analysis of a 5′-deletion mutant revealed a negative -regulatory element located within the E2 ORF. The HPV-16 early poly(A) signal is located downstream of the critical promoter region. Inactivation of this element by site-directed mutagenesis strongly enhanced luciferase activity. However, mutation of two potential TATA-binding protein (TBP) sites located within the critical promoter region did not abolish the activity. Altogether, these data indicate the possibility of a TATA-less promoter in the HPV-16 and HPV-18 LURs. Together with the early poly(A) signal, this potential promoter might be involved in the differentiation-dependent regulation of late gene expression.

  • Received:
  • Accepted:
  • Published Online:
© Journal of General Virology 1996
Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-77-9-2193
1996-09-01
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/jgv/77/9/JV0770092193.html?itemId=/content/journal/jgv/10.1099/0022-1317-77-9-2193&mimeType=html&fmt=ahah

References

  1. Andrews E. M., DiMaio D. 1993; Hierarchy of polyadenylation site usage by bovine papillomavirus in transformed mouse cells. Journal of Virology 67:7705–7710
     [Google Scholar]
  2. Baker C. C., Howley P. M. 1987; Differential promoter utilization by the bovine papillomavirus in transformed cells and productively infected wart tissues. EMBO Journal 6:1027–1035
     [Google Scholar]
  3. Baker C. C., Noe J. S. 1989; Transcriptional termination between bovine papillomavirus type 1 (BPV-1) early and late polyadenylation sites blocks late transcription in BPV-l-transformed cells. Journal of Virology 63:3529–3534
     [Google Scholar]
  4. Bedell M. A., Hudson J. B., Golub T. R., Turyk M. E., Hosken M., Wilbanks G. D., Laimins L. A. 1991; Amplification of human papillomavirus genomes in vitro is dependent on epithelial differentiation. Journal of Virology 65:2254–2260
     [Google Scholar]
  5. Beyer-Finkler E., Stoler M. H., Girardi F., Pfister H. 1990; Cell differentiation-related gene expression of human papillomavirus 33. Medical Microbiology and Immunology, Berlin 179:185–192
     [Google Scholar]
  6. Bosch F. X., Manos M. M., Munoz N., Sherman M., Jansen A. M., Peto J., Schiffman M. H., Moreno V., Kurman R., Shah K. V. 1995; Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. International Biological Study on Cervical Cancer (IBSCC) Study Group. Journal of the National Cancer Institute 87:796–802
     [Google Scholar]
  7. Brasier A. R., Tate J. E., Habener J. F. 1989; Optimized use of the firefly luciferase assay as a reporter gene in mammalian cell lines. BioTechniques 7:1116–1122
     [Google Scholar]
  8. Chen C., Okayama H. 1987; High-efficiency transformation of mammalian cells by plasmid DNA. Molecular and Cellular Biology 7:2745–2752
     [Google Scholar]
  9. Chow L. T., Nasseri M., Wolinsky S. M., Broker T. R. 1987a; Human papillomavirus types 6 and 11 mRNAs from genital condylomata acuminata. Journal of Virology 61:2581–2588
     [Google Scholar]
  10. Chow L. T., Reilly S. S., Broker T. R., Taichman L. B. 1987b; Identification and mapping of human papillomavirus type 1 RNA transcripts recovered from plantar warts and infected epithelial cell cultures. Journal of Virology 61:1913–1918
     [Google Scholar]
  11. Cole S. T., Danos O. 1987; Nucleotide sequence and comparative analysis of the human papillomavirus type 18 genome. Phytogeny of papillomaviruses and repeated structure of the E6 and E7 gene products. Journal of Molecular Biology 193:599–608
     [Google Scholar]
  12. Darnell J. E., Lodish H., Baltimore D. 1990 Molecular Cell Biology New York: Scientific American Books;
     [Google Scholar]
  13. Descombes P., Chojker M., Lichtsteiner S., Falvey E., Schibler U. 1990; LAP, a novel member of the C/EBP gene family, encodes a liver-enriched transcriptional activator protein. Genes and Development 4:1451–1551
     [Google Scholar]
  14. de Villiers E. M. 1994; Human pathogenic papillomavirus types: an update. Current Topics in Microbiology and Immunology 186:1–12
     [Google Scholar]
  15. DeWet J. R., Wood K. V., DeLuca M., Helinski D. R., Subramani S. 1987; Firefly luciferase gene: structure and expression in mammalian cells. Molecular and Cellular Biology 7:725–737
     [Google Scholar]
  16. Dürst M., Glitz D., Schneider A., zur Hausen H. 1992; Human papillomavirus type 16 (HPV 16) gene expression and DNA replication in cervical neoplasia: analysis by in situ hybridization. Virology 189:132–140
     [Google Scholar]
  17. Geisen C. 1993 Die Genomregion E5 der humanen Papillomvirus-Typen 16 und 18: Analyse eines E5-verwandten Abschnittes des humanen Genoms und Charakterisierung von Promotoreigenschaften der oiralen Sequenzen PhD thesis Deutsches Krebsforschungszentrum & Universität Bonn;
     [Google Scholar]
  18. Geisen C., Delius H., Lichter P., Kahn T. 1995; A transcribed human sequence related to the mouse HC1 and the human papillomavirus type 18 E5 genes is located at chromosome 7p13–14. Human Molecular Genetics 4:1337–1345
     [Google Scholar]
  19. Guarente L. 1987; Regulatory proteins in yeast. Annual Review of Genetics 21:425–452
     [Google Scholar]
  20. Halbert C. L., Galloway D. A. 1988; Identification of the E5 open reading frame of human papillomavirus type 16. Journal of Virology 62:1071–1075
     [Google Scholar]
  21. Hoppe-Seyler F., Butz K. 1992; Activation of human papillomavirus type 18 E6-E7 oncogene expression by transcription factor Spl. Nucleic Acids Research 20:6701–6706
     [Google Scholar]
  22. Hoppe-Seyler F., Butz K., zur Hausen H. 1991; Repression of the human papillomavirus type 18 enhancer by the cellular transcription factor Oct-1. Journal of Virology 65:5613–5618
     [Google Scholar]
  23. Hummel M., Lim H. B., Laimins L. A. 1995; Human papillomavirus type 31b late gene expression is regulated through protein kinase C-mediated changes in RNA processing. Journal of Virology 69:3381–3388
     [Google Scholar]
  24. Kahn T., Friesl H., Copeland N. G., Gilbert D. J., Jenkins N. A., Gissmann L., Kramer J., zur Hausen H. 1992; Molecular cloning, analysis, and chromosomal localization of a mouse genomic sequence related to the human papillomavirus type 18 E5 region. Molecular Carcinogenesis 6:88–99
     [Google Scholar]
  25. Karlen S., Offord E. A., Beard P. 1996; Functional promoters in the genome of human papillomavirus type 6b. Journal of General Virology 77:11–16
     [Google Scholar]
  26. Luckow B., Schiitz G. 1987; CAT constructions with multiple unique restriction sites for the functional analysis of eukaryotic promoters and regulatory elements. Nucleic Acid Research 15:5490–5495
     [Google Scholar]
  27. Maki H., Fujikawa-Adachi K., Yoshie O. 1996; Evidence for a promoter-like activity in the short non-coding region of human papillomaviruses. Journal of General Virology 77:453–458
     [Google Scholar]
  28. Maniatis T., Goodbourn S., Fischer J. A. 1987; Regulation of inducible and tissue-specific gene expression. Science 236:1237–1245
     [Google Scholar]
  29. Maniatis T., Fritsch E. F., Sambrook J. 1989 Molecular Cloning: a Laboratory Manual New York: Cold Spring Harbor Laboratory Press;
     [Google Scholar]
  30. Palermo-Dilts D. A., Broker T. R., Chow L. T. 1990; Human papillomavirus type 1 produces redundant as well as polycistronic mRNAs in plantar warts. Journal of Virology 64:3144–3149
     [Google Scholar]
  31. Proudfoot N. 1991; Poly(A) signals. Cell 64:671–674
     [Google Scholar]
  32. Rohlfs M., Winkenbach S., Meyer S., Rupp T., Dürst M. 1991; Viral transcription in human keratinocyte cell lines immortalized by human papillomavirus type-16. Virology 183:331–342
     [Google Scholar]
  33. Seedorf K., Krammer G., Durst M., Suhai S., Rowekamp W. G. 1985; Human papillomavirus type 16 DNA sequence. Virology 145:181–185
     [Google Scholar]
  34. Shah K. V., Howley P. M. 1990; Papillomaviruses. In Virology pp 1651–1676 Edited by Fields B. N., Knipe D. M. New York: Raven Press;
     [Google Scholar]
  35. Sherman L., Alloul N., Golan I., Diirst M., Baram A. 1992; Expression and splicing patterns of human papillomavirus type-16 mRNAs in pre-cancerous lesions and carcinomas of the cervix, in human keratinocytes immortalized by HPV 16, and in cell lines established from cervical cancers. International Journal of Cancer 50:356–364
     [Google Scholar]
  36. Stoler M. H., Wolinsky S. M., Whitbeck A., Broker T. R., Chow L. T. 1989; Differentiation-linked human papillomavirus types 6 and 11 transcription in genital condylomata revealed by in situ hybridization with message-specific RNA probes. Virology 172:331–340
     [Google Scholar]
  37. Stoler M. H., Rhodes C. R., Whitbeck A., Wolinsky S. M., Chow L. T., Broker T. R. 1992; Human papillomavirus type 16 and 18 gene expression in cervical neoplasias. Human Pathology 23:117–128
     [Google Scholar]
  38. Stubenrauch F., Malejczyk J., Fuchs P. G., Pfister H. 1992; Late promoter of human papillomavirus type 8 and its regulation. Journal of Virology 66:3485–3493
     [Google Scholar]
  39. Wagner S., Cullmann G., Knippers R. 1991; The Q300 gene: a novel transcription unit induced in simian virus 40-infected and -transformed mouse cells. Journal of Virology 65:3259–3267
     [Google Scholar]
  40. Wettstein F. O., Barbosa M. S., Nasseri M. 1987; Identification of the major cottontail rabbit papillomavirus late RNA cap site and mapping and quantitation of an E2 and minor E6 coding mRNA in papillomas and carcinomas. Virology 159:321–328
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-77-9-2193
Loading
Promoter Activity of Sequences Located Upstream of the Human Papillomavirus Types 16 and 18 Late Regions
J. Gen. Virol. 77, 2193 (1996); https://doi.org/10.1099/0022-1317-77-9-2193
/content/journal/jgv/10.1099/0022-1317-77-9-2193
/content/journal/jgv/10.1099/0022-1317-77-9-2193
Loading

Data & Media loading...

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error