1887

Abstract

Persistent infections with high-risk human papillomaviruses (HPVs) can result in the development of cancer of the cervix uteri and other malignancies. The underlying molecular mechanisms leading to the progression of HPV-induced lesions are, however, not well understood. Cottontail rabbit papillomavirus (CRPV) induces papillomas in domestic rabbits which progress at a very high rate to cancer. Using this model, we compared the transcriptional patterns of CRPV in papillomas and carcinomas by RNA sequencing (RNA-seq). The most abundant transcripts can encode E7, short E6 and E1^E4, followed by full-length E6, E2, E1 and E9^E2C. In addition, we identified two rare, novel splice junctions 7810/3714 and 1751/3065 in both papillomas and carcinomas which have been described for other papillomaviruses. Neither RNA-seq nor quantitative real-time PCR-based assays identified qualitative or quantitative changes of viral transcription between papillomas and carcinomas. In summary, our analyses confirmed that papillomaviruses have highly similar transcriptional patterns, but they do not suggest that changes in these patterns contribute to the progression of CRPV-induced tumours.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.000239
2015-10-01
2024-03-29
Loading full text...

Full text loading...

/deliver/fulltext/jgv/96/10/3083.html?itemId=/content/journal/jgv/10.1099/jgv.0.000239&mimeType=html&fmt=ahah

References

  1. Baker C.C., Howley P.M. 1987; Differential promoter utilization by the bovine papillomavirus in transformed cells and productively infected wart tissues. EMBO J 6:1027–1035
    [Google Scholar]
  2. Bergvall M., Melendy T., Archambault J. 2013; The E1 proteins. Virology 445:35–56 [View Article][PubMed]
    [Google Scholar]
  3. Cancer Genome Atlas N. 2015; Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature 517:576–582 [CrossRef]
    [Google Scholar]
  4. Chen J., Xue Y., Poidinger M., Lim T., Chew S.H., Pang C.L., Abastado J.P., Thierry F. 2014; Mapping of HPV transcripts in four human cervical lesions using RNAseq suggests quantitative rearrangements during carcinogenic progression. Virology 462-463:14–24 [View Article][PubMed]
    [Google Scholar]
  5. Choe J., Vaillancourt P., Stenlund A., Botchan M. 1989; Bovine papillomavirus type 1 encodes two forms of a transcriptional repressor: structural and functional analysis of new viral cDNAs. J Virol 63:1743–1755
    [Google Scholar]
  6. Chow L.T., Reilly S.S., Broker T.R., Taichman L.B. 1987; Identification and mapping of human papillomavirus type 1 RNA transcripts recovered from plantar warts and infected epithelial cell cultures. J Virol 61:1913–1918
    [Google Scholar]
  7. DiMaio D., Petti L.M. 2013; The E5 proteins. Virology 445:99–114 [View Article][PubMed]
    [Google Scholar]
  8. Dobin A., Davis C.A., Schlesinger F., Drenkow J., Zaleski C., Jha S., Batut P., Chaisson M., Gingeras T.R. 2013; star: ultrafast universal RNA-seq aligner. Bioinformatics 29:15–21 [View Article][PubMed]
    [Google Scholar]
  9. Doorbar J. 2013; The E4 protein; structure, function and patterns of expression. Virology 445:80–98 [View Article][PubMed]
    [Google Scholar]
  10. Ganzenmueller T., Matthaei M., Muench P., Scheible M., Iftner A., Hiller T., Leiprecht N., Probst S., Stubenrauch F., Iftner T. 2008; The E7 protein of the cottontail rabbit papillomavirus immortalizes normal rabbit keratinocytes and reduces pRb levels, while E6 cooperates in immortalization but neither degrades p53 nor binds E6AP. Virology 372:313–324 [View Article][PubMed]
    [Google Scholar]
  11. Haedicke J., Iftner T. 2013; Human papillomaviruses and cancer. Radiother Oncol 108:397–402 [View Article]
    [Google Scholar]
  12. Häfner N., Driesch C., Gajda M., Jansen L., Kirchmayr R., Runnebaum I.B., Dürst M. 2008; Integration of the HPV16 genome does not invariably result in high levels of viral oncogene transcripts. Oncogene 27:1610–1617 [View Article][PubMed]
    [Google Scholar]
  13. Haller K., Stubenrauch F., Pfister H. 1995; Differentiation-dependent transcription of the epidermodysplasia verruciformis-associated human papillomavirus type 5 in benign lesions. Virology 214:245–255 [View Article][PubMed]
    [Google Scholar]
  14. Jeckel S., Huber E., Stubenrauch F., Iftner T. 2002; A transactivator function of cottontail rabbit papillomavirus E2 is essential for tumor induction in rabbits. J Virol 76:11209–11215 [View Article][PubMed]
    [Google Scholar]
  15. Jeckel S., Loetzsch E., Huber E., Stubenrauch F., Iftner T. 2003; Identification of the E9/E2C cDNA and functional characterization of the gene product reveal a new repressor of transcription and replication in cottontail rabbit papillomavirus. J Virol 77:8736–8744 [View Article][PubMed]
    [Google Scholar]
  16. Lambert P.F., Pan H., Pitot H.C., Liem A., Jackson M., Griep A.E. 1993; Epidermal cancer associated with expression of human papillomavirus type 16 E6 and E7 oncogenes in the skin of transgenic mice. Proc Natl Acad Sci U S A 90:5583–5587 [View Article][PubMed]
    [Google Scholar]
  17. Leiprecht N., Notz E., Schuetz J., Haedicke J., Stubenrauch F., Iftner T. 2014; A novel recombinant papillomavirus genome enabling in vivo RNA interference reveals that YB-1, which interacts with the viral regulatory protein E2, is required for CRPV-induced tumor formation in vivo . Am J Cancer Res 4:222–233
    [Google Scholar]
  18. Li H., Handsaker B., Wysoker A., Fennell T., Ruan J., Homer N., Marth G., Abecasis G., Durbin R. 2009; 1000 Genome Project Data Processing Subgroup, The Sequence Alignment/Map format and SAMtools. Bioinformatics 25:2078–2079 [View Article][PubMed]
    [Google Scholar]
  19. Martin M. 2012; Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnet.journal 17:10–12 [CrossRef]
    [Google Scholar]
  20. McBride A.A. 2013; The papillomavirus E2 proteins. Virology 445:57–79 [View Article][PubMed]
    [Google Scholar]
  21. Meyers C., Harry J., Lin Y.L., Wettstein F.O. 1992; Identification of three transforming proteins encoded by cottontail rabbit papillomavirus. J Virol 66:1655–1664
    [Google Scholar]
  22. Moody C.A., Laimins L.A. 2010; Human papillomavirus oncoproteins: pathways to transformation. Nat Rev Cancer 10:550–560 [View Article][PubMed]
    [Google Scholar]
  23. Muench P., Probst S., Schuetz J., Leiprecht N., Busch M., Wesselborg S., Stubenrauch F., Iftner T. 2010; Cutaneous papillomavirus E6 proteins must interact with p300 and block p53-mediated apoptosis for cellular immortalization and tumorigenesis. Cancer Res 70:6913–6924 [View Article][PubMed]
    [Google Scholar]
  24. Nasseri M., Wettstein F.O. 1984; Differences exist between viral transcripts in cottontail rabbit papillomavirus-induced benign and malignant tumors as well as non-virus-producing and virus-producing tumors. J Virol 51:706–712
    [Google Scholar]
  25. Ojesina A.I., Lichtenstein L., Freeman S.S., Pedamallu C.S., Imaz-Rosshandler I., Pugh T.J., Cherniack A.D., Ambrogio L., Cibulskis K., other authors. 2014; Landscape of genomic alterations in cervical carcinomas. Nature 506:371–375 [View Article][PubMed]
    [Google Scholar]
  26. Phelps W.C., Leary S.L., Faras A.J. 1985; Shope papillomavirus transcription in benign and malignant rabbit tumors. Virology 146:120–129 [View Article][PubMed]
    [Google Scholar]
  27. Probst S., Notz E., Wolff M., Buehlmann J., Stubenrauch F., Iftner T. 2013; A recombinant cottontail rabbit papillomavirus genome for ectopic expression of genes in cells infected with virus in vivo . J Virol Methods 187:110–113 [View Article][PubMed]
    [Google Scholar]
  28. Robinson J.T., Thorvaldsdóttir H., Winckler W., Guttman M., Lander E.S., Getz G., Mesirov J.P. 2011; Integrative genomics viewer. Nat Biotechnol 29:24–26 [View Article][PubMed]
    [Google Scholar]
  29. Sankovski E., Männik A., Geimanen J., Ustav E., Ustav M. 2014; Mapping of betapapillomavirus human papillomavirus 5 transcription and characterization of viral-genome replication function. J Virol 88:961–973 [View Article][PubMed]
    [Google Scholar]
  30. Schmitt A., Harry J.B., Rapp B., Wettstein F.O., Iftner T. 1994; Comparison of the properties of the E6 and E7 genes of low- and high-risk cutaneous papillomaviruses reveals strongly transforming and high Rb-binding activity for the E7 protein of the low-risk human papillomavirus type 1. J Virol 68:7051–7059
    [Google Scholar]
  31. Steenbergen R.D., Snijders P.J., Heideman D.A., Meijer C.J. 2014; Clinical implications of (epi)genetic changes in HPV-induced cervical precancerous lesions. Nat Rev Cancer 14:395–405 [View Article][PubMed]
    [Google Scholar]
  32. Straub E., Fertey J., Dreer M., Iftner T., Stubenrauch F. 2015; Characterization of the Human Papillomavirus 16 E8 Promoter. J Virol 89:7304–13 [CrossRef]
    [Google Scholar]
  33. Stubenrauch F., Malejczyk J., Fuchs P.G., Pfister H. 1992; Late promoter of human papillomavirus type 8 and its regulation. J Virol 66:3485–3493
    [Google Scholar]
  34. 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 [View Article][PubMed]
    [Google Scholar]
  35. Wu X., Xiao W., Brandsma J.L. 1994; Papilloma formation by cottontail rabbit papillomavirus requires E1 and E2 regulatory genes in addition to E6 and E7 transforming genes. J Virol 68:6097–6102
    [Google Scholar]
  36. Zeltner R., Borenstein L.A., Wettstein F.O., Iftner T. 1994; Changes in RNA expression pattern during the malignant progression of cottontail rabbit papillomavirus-induced tumors in rabbits. J Virol 68:3620–3630
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.000239
Loading
/content/journal/jgv/10.1099/jgv.0.000239
Loading

Data & Media loading...

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