1887

Abstract

SP100 proteins are components of nuclear domain 10 structures and have been implicated as inhibitors of human papillomavirus (HPV) replication. In this study, we have addressed the role of SP100 in tumour formation by the cottontail rabbit () papillomavirus (CRPV or SfPV1) in a rabbit model. Tissue culture studies using rabbit keratinocyte lines indicated that rabbit SP100 is an interferon-beta-inducible gene similar to its human counterpart. Stable knockdown of SP100 by shRNA in a cell line harbouring CRPV genomes resulted in a decrease of viral early transcripts. In contrast, infection of domestic rabbits with recombinant CRPV genomes expressing short hairpin (sh)RNAs directed against SP100 did not reveal changes in tumour formation rate, tumour size or early viral transcript levels. However, late viral transcript levels and viral genome copies were consistently lower in CRPV/shSP100-induced tumours than in the control, but these differences did not reach statistical significance. In summary, this study suggests that rabbit SP100 is not an inhibitor but an activator of CRPV replication and transcription.

Keyword(s): papillomavirus , SfPV1 , shRNA , SP100 and transcription
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2018-03-01
2024-04-26
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References

  1. Parkin DM, Bray F. Chapter 2: The burden of HPV-related cancers. Vaccine 2006; 24:S11–S25 [View Article][PubMed]
    [Google Scholar]
  2. Stubenrauch F, Laimins LA. Human papillomavirus life cycle: active and latent phases. Semin Cancer Biol 1999; 9:379–386 [View Article][PubMed]
    [Google Scholar]
  3. Scherer M, Stamminger T. Emerging role of PML nuclear bodies in innate immune signaling. J Virol 2016; 90:5850–5854 [View Article][PubMed]
    [Google Scholar]
  4. Tavalai N, Stamminger T. New insights into the role of the subnuclear structure ND10 for viral infection. Biochim Biophys Acta 2008; 1783:2207–2221 [View Article][PubMed]
    [Google Scholar]
  5. Bienkowska-Haba M, Luszczek W, Keiffer TR, Guion LGM, Digiuseppe S et al. Incoming human papillomavirus 16 genome is lost in PML protein-deficient HaCaT keratinocytes. Cell Microbiol 2017; 19:e12708 [View Article][PubMed]
    [Google Scholar]
  6. Day PM, Baker CC, Lowy DR, Schiller JT. Establishment of papillomavirus infection is enhanced by promyelocytic leukemia protein (PML) expression. Proc Natl Acad Sci USA 2004; 101:14252–14257 [View Article][PubMed]
    [Google Scholar]
  7. Stepp WH, Meyers JM, McBride AA. Sp100 provides intrinsic immunity against human papillomavirus infection. MBio 2013; 4:e00845-13 [View Article][PubMed]
    [Google Scholar]
  8. Habiger C, Jäger G, Walter M, Iftner T, Stubenrauch F. Interferon Kappa inhibits human papillomavirus 31 transcription by inducing Sp100 proteins. J Virol 2015; 90:694–704 [View Article][PubMed]
    [Google Scholar]
  9. Stepp WH, Stamos JD, Khurana S, Warburton A, McBride AA. Sp100 colocalizes with HPV replication foci and restricts the productive stage of the infectious cycle. PLoS Pathog 2017; 13:e1006660 [View Article][PubMed]
    [Google Scholar]
  10. Guldner HH, Szostecki C, Schröder P, Matschl U, Jensen K et al. Splice variants of the nuclear dot-associated Sp100 protein contain homologies to HMG-1 and a human nuclear phosphoprotein-box motif. J Cell Sci 1999; 112:733–747[PubMed]
    [Google Scholar]
  11. Shope RE, Hurst EW. Infectious papillomatosis of rabbits : with a note on the histopathology. J Exp Med 1933; 58:607–624 [View Article][PubMed]
    [Google Scholar]
  12. Hu J, Budgeon LR, Cladel NM, Culp TD, Balogh KK et al. Detection of L1, infectious virions and anti-L1 antibody in domestic rabbits infected with cottontail rabbit papillomavirus. J Gen Virol 2007; 88:3286–3293 [View Article][PubMed]
    [Google Scholar]
  13. Peh WL, Brandsma JL, Christensen ND, Cladel NM, Wu X et al. The viral E4 protein is required for the completion of the cottontail rabbit papillomavirus productive cycle in vivo. J Virol 2004; 78:2142–2151 [View Article][PubMed]
    [Google Scholar]
  14. Probst-Hunczek S, Jäger G, Schneider M, Notz E, Stubenrauch F et al. RNA sequencing analysis identifies novel spliced transcripts but does not indicate quantitative or qualitative changes of viral transcripts during progression of cottontail rabbit papillomavirus-induced tumours. J Gen Virol 2015; 96:3083–3089 [View Article][PubMed]
    [Google Scholar]
  15. Wettstein FO, Barbosa MS, Nasseri M. 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 1987; 159:321–328 [View Article][PubMed]
    [Google Scholar]
  16. Zeltner R, Borenstein LA, Wettstein FO, Iftner T. Changes in RNA expression pattern during the malignant progression of cottontail rabbit papillomavirus-induced tumors in rabbits. J Virol 1994; 68:3620–3630[PubMed]
    [Google Scholar]
  17. Delcuratolo M, Fertey J, Schneider M, Schuetz J, Leiprecht N et al. Papillomavirus-associated tumor formation critically depends on c-Fos expression induced by viral protein E2 and bromodomain protein Brd4. PLoS Pathog 2016; 12:e1005366 [View Article][PubMed]
    [Google Scholar]
  18. Leiprecht N, Notz E, Schuetz J, Haedicke J, Stubenrauch F et al. 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 2014; 4:222–233[PubMed]
    [Google Scholar]
  19. Guldner HH, Szostecki C, Grötzinger T, Will H. IFN enhance expression of Sp100, an autoantigen in primary biliary cirrhosis. J Immunol 1992; 149:4067–4073[PubMed]
    [Google Scholar]
  20. Negorev DG, Vladimirova OV, Ivanov A, Rauscher F, Maul GG. Differential role of Sp100 isoforms in interferon-mediated repression of herpes simplex virus type 1 immediate-early protein expression. J Virol 2006; 80:8019–8029 [View Article][PubMed]
    [Google Scholar]
  21. Negorev DG, Vladimirova OV, Maul GG. Differential functions of interferon-upregulated Sp100 isoforms: herpes simplex virus type 1 promoter-based immediate-early gene suppression and PML protection from ICP0-mediated degradation. J Virol 2009; 83:5168–5180 [View Article][PubMed]
    [Google Scholar]
  22. Chang YE, Pena L, Sen GC, Park JK, Laimins LA. Long-term effect of interferon on keratinocytes that maintain human papillomavirus type 31. J Virol 2002; 76:8864–8874 [View Article][PubMed]
    [Google Scholar]
  23. Spink KM, Laimins LA. Induction of the human papillomavirus type 31 late promoter requires differentiation but not DNA amplification. J Virol 2005; 79:4918–4926 [View Article][PubMed]
    [Google Scholar]
  24. Sternsdorf T, Jensen K, Reich B, Will H. The nuclear dot protein sp100, characterization of domains necessary for dimerization, subcellular localization, and modification by small ubiquitin-like modifiers. J Biol Chem 1999; 274:12555–12566 [View Article][PubMed]
    [Google Scholar]
  25. Brummelkamp TR, Bernards R, Agami R. A system for stable expression of short interfering RNAs in mammalian cells. Science 2002; 296:550–553 [View Article][PubMed]
    [Google Scholar]
  26. Probst S, Notz E, Wolff M, Buehlmann J, Stubenrauch F et al. A recombinant cottontail rabbit papillomavirus genome for ectopic expression of genes in cells infected with virus in vivo. J Virol Methods 2013; 187:110–113 [View Article][PubMed]
    [Google Scholar]
  27. Pfaffl MW. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 2001; 29:e45 [View Article][PubMed]
    [Google Scholar]
  28. Huber E, Vlasny D, Jeckel S, Stubenrauch F, Iftner T. Gene profiling of cottontail rabbit papillomavirus-induced carcinomas identifies upregulated genes directly Involved in stroma invasion as shown by small interfering RNA-mediated gene silencing. J Virol 2004; 78:7478–7489 [View Article][PubMed]
    [Google Scholar]
  29. Jeckel S, Loetzsch E, Huber E, Stubenrauch F, Iftner T. 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 2003; 77:8736–8744 [View Article][PubMed]
    [Google Scholar]
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