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. 1994 Jun;144(6):1167–1171.

Latent infection induced with cottontail rabbit papillomavirus. A model for human papillomavirus latency.

C A Amella 1, L A Lofgren 1, A M Ronn 1, M Nouri 1, M J Shikowitz 1, B M Steinberg 1
PMCID: PMC1887472  PMID: 8203458

Abstract

Latent human papillomavirus infection, a very common event, is most likely the source of primary and recurrent papillomas of the respiratory and genital tracts and might also be the source of neoplastic lesions of the female genital tract and the penis. We have developed a simple model for papillomavirus latency using cottontail rabbit papillomavirus. Skin of domestic rabbits was minimally scarified and inoculated with dilutions of a crude virus suspension ranging from 200 ng to 20 pg viral DNA per inoculated site. Dilution of virus to less than 10 ng/site resulted in delayed and reduced efficiency of inducing warts. After follow-up of 1 to 6 months, sites immediately adjacent to papillomas and inoculated sites where papillomas did not form were biopsied and analyzed by Southern blot and polymerase chain reaction. Inoculated tissues that were clinically and histologically normal contained viral DNA at low levels, detectable by polymerase chain reaction. Ability of the latent virus to induce warts was confirmed by activation with mild skin irritation causing wart formation. This simple model system for latent papillomavirus can be used to study mechanisms of viral activation, therapies to prevent activation, and therapies to eliminate latent virus and thus cure the infection.

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Selected References

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  1. Abramson A. L., DiLorenzo T. P., Steinberg B. M. Is papillomavirus detectable in the plume of laser-treated laryngeal papilloma? Arch Otolaryngol Head Neck Surg. 1990 May;116(5):604–607. doi: 10.1001/archotol.1990.01870050104017. [DOI] [PubMed] [Google Scholar]
  2. Amtmann E., Volm M., Wayss K. Tumour induction in the rodent Mastomys natalensis by activation of endogenous papilloma virus genomes. Nature. 1984 Mar 15;308(5956):291–292. doi: 10.1038/308291a0. [DOI] [PubMed] [Google Scholar]
  3. Ferenczy A., Mitao M., Nagai N., Silverstein S. J., Crum C. P. Latent papillomavirus and recurring genital warts. N Engl J Med. 1985 Sep 26;313(13):784–788. doi: 10.1056/NEJM198509263131304. [DOI] [PubMed] [Google Scholar]
  4. Gissmann L., Wolnik L., Ikenberg H., Koldovsky U., Schnürch H. G., zur Hausen H. Human papillomavirus types 6 and 11 DNA sequences in genital and laryngeal papillomas and in some cervical cancers. Proc Natl Acad Sci U S A. 1983 Jan;80(2):560–563. doi: 10.1073/pnas.80.2.560. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Kreider J. W., Bartlett G. L. The Shope papilloma-carcinoma complex of rabbits: a model system of neoplastic progression and spontaneous regression. Adv Cancer Res. 1981;35:81–110. doi: 10.1016/s0065-230x(08)60909-4. [DOI] [PubMed] [Google Scholar]
  6. Lacey M., Alpert S., Hanahan D. Bovine papillomavirus genome elicits skin tumours in transgenic mice. Nature. 1986 Aug 14;322(6080):609–612. doi: 10.1038/322609a0. [DOI] [PubMed] [Google Scholar]
  7. Mounts P., Shah K. V., Kashima H. Viral etiology of juvenile- and adult-onset squamous papilloma of the larynx. Proc Natl Acad Sci U S A. 1982 Sep;79(17):5425–5429. doi: 10.1073/pnas.79.17.5425. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. ROGERS S., ROUS P. Joint action of a chemical carcinogen and a neoplastic virus to induce cancer in rabbits; results of exposing epidermal cells to a carcinogenic hydrocarbon at time of infection with the Shope papilloma virus. J Exp Med. 1951 May;93(5):459–488. doi: 10.1084/jem.93.5.459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Rock D. L., Fraser N. W. Detection of HSV-1 genome in central nervous system of latently infected mice. Nature. 1983 Apr 7;302(5908):523–525. doi: 10.1038/302523a0. [DOI] [PubMed] [Google Scholar]
  10. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
  11. Shikowitz M. J., Steinberg B. M., Abramson A. L. Hematoporphyrin derivative therapy of papillomas. Experimental study. Arch Otolaryngol Head Neck Surg. 1986 Jan;112(1):42–46. doi: 10.1001/archotol.1986.03780010044007. [DOI] [PubMed] [Google Scholar]
  12. Siegsmund M., Wayss K., Amtmann E. Activation of latent papillomavirus genomes by chronic mechanical irritation. J Gen Virol. 1991 Nov;72(Pt 11):2787–2789. doi: 10.1099/0022-1317-72-11-2787. [DOI] [PubMed] [Google Scholar]
  13. Steinberg B. M., Topp W. C., Schneider P. S., Abramson A. L. Laryngeal papillomavirus infection during clinical remission. N Engl J Med. 1983 May 26;308(21):1261–1264. doi: 10.1056/NEJM198305263082104. [DOI] [PubMed] [Google Scholar]
  14. Stevens J. G. Human herpesviruses: a consideration of the latent state. Microbiol Rev. 1989 Sep;53(3):318–332. doi: 10.1128/mr.53.3.318-332.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]

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