Large cutaneous rabbit papillomas that persist during cyclosporin A treatment can regress spontaneously after cessation of immunosuppression Free

Abstract

Cottontail rabbit papillomavirus (CRPV)-induced papillomas can progress into malignant carcinomas, remain persistent or regress. Both host immunity and virus genetic background play critical roles in these events. To test how host immunity influences CRPV-induced papilloma evolution, both EIII/JC (inbred) and New Zealand White (outbred) rabbits were treated with an immunosuppressive drug, cyclosporin A (CsA), for 80 days and the regression of three regressive constructs, H.CRPVr (a CRPV regressive strain), H.CRPVp-E6r (a progressive strain with regressive E6) and H.CRPVp-CE6rm (H.CRPVp with the carboxyl terminal of regressive E6, containing mutations at amino acid residues E252G, G258D and S259P) was checked. Papillomas induced by H.CRPVr and H.CRPVp-E6r on control inbred and outbred rabbits regressed totally around week 8, whereas papillomas on all CsA-treated rabbits grew progressively. After cessation of CsA treatment, papillomas began to regress in six outbred rabbits: 14 of 18 papillomas induced by CRPVr, 11 of 18 papillomas induced by H.CRPVp-E6r and eight of 10 papillomas induced by H.CRPVp-CE6rm regressed around week 21. In four CsA-treated inbred rabbits, two of 17 papillomas induced by H.CRPVr and one of 17 papillomas induced by H.CRPVp-E6r regressed. These data indicate that papillomas induced by a regressive CRPV strain can become persistent in the transiently immunosuppressed host. However, returning immunity can lead to regression and clearance of large papillomas (with increased antigenicity) in an outbred population, whilst these same antigenic papillomas persist in inbred rabbits.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.80448-0
2005-01-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/jgv/86/1/vir860055.html?itemId=/content/journal/jgv/10.1099/vir.0.80448-0&mimeType=html&fmt=ahah

References

  1. Ali A. T. M. M., Morley J., Rumjanek V. M. 1982; Cyclosporin-A inhibits accumulation of lymphocytes within lymph nodes. Immunology 47:345–349
    [Google Scholar]
  2. Andrus L., Lafferty K. J. 1981; Inhibition of T-cell activity by cyclosporin A. Scand J Immunol 15:449–458
    [Google Scholar]
  3. Bavinck J. N., Gissman L., Claas F. H. 7 other authors 1993; Relation between skin cancer, humoral responses to human papillomaviruses, and HLA class II molecules in renal transplant recipients. J Immunol 151:1579–1586
    [Google Scholar]
  4. Brandsma J. L. 1994; Animal models of human-papillomavirus-associated oncogenesis. Intervirology 37:189–200
    [Google Scholar]
  5. Breitburd F., Ramoz N., Salmon J., Orth G. 1996; HLA control in the progression of human papillomavirus infections. Semin Cancer Biol 7:359–371 [CrossRef]
    [Google Scholar]
  6. Christensen N. D., Han R., Kreider J. W. 1999; Cottontail rabbit papillomavirus. In Persistent Viral Infections pp  485–502 Edited by Ahmed R., Chen I. S. Y. Chichester, UK: Wiley;
    [Google Scholar]
  7. Davidson E. J., Davidson J. A., Sterling J. C., Baldwin P. J. W., Kitchener H. C., Stern P. L. 2003; Association between human leukocyte antigen polymorphism and human papillomavirus 16-positive vulval intraepithelial neoplasia in British women. Cancer Res 63:400–403
    [Google Scholar]
  8. Dupont E., Huygen K., Schandene L., Vandercruys M., Palfliet K., Wybran J. 1985; Influence of in vivo immunosuppressive drugs on production of lymphokines. Transplantation 39:143–147 [CrossRef]
    [Google Scholar]
  9. Euvrard S., Kanitakis J., Claudy A. 2003; Skin cancers after organ transplantation. N Engl J Med 348:1681–1691 [CrossRef]
    [Google Scholar]
  10. Furumoto H., Irahara M. 2002; Human papilloma virus (HPV) and cervical cancer. J Med Invest 49:124–133
    [Google Scholar]
  11. Han R., Breitburd F., Marche P. N., Orth G. 1992; Linkage of regression and malignant conversion of rabbit viral papillomas to MHC class II genes. Nature 356:66–68 [CrossRef]
    [Google Scholar]
  12. Han R., Cladel N. M., Reed C. A., Peng X., Christensen N. D. 1999; Protection of rabbits from viral challenge by gene gun-based intracutaneous vaccination with a combination of cottontail rabbit papillomavirus E1, E2, E6, and E7 genes. J Virol 73:7039–7043
    [Google Scholar]
  13. Hu J., Cladel N. M., Pickel M. D., Christensen N. D. 2002a; Amino acid residues in the carboxy-terminal region of cottontail rabbit papillomavirus E6 influence spontaneous regression of cutaneous papillomas. J Virol 76:11801–11808 [CrossRef]
    [Google Scholar]
  14. Hu J., Han R., Cladel N. M., Pickel M. D., Christensen N. D. 2002b; Intracutaneous DNA vaccination with the E8 gene of cottontail rabbit papillomavirus induces protective immunity against virus challenge in rabbits. J Virol 76:6453–6459 [CrossRef]
    [Google Scholar]
  15. Jenkins M. K., Schwartz R. H., Pardoll D. M. 1988; Effects of cyclosporine A on T cell development and clonal deletion. Science 241:1655–1658 [CrossRef]
    [Google Scholar]
  16. Orth G., Favre M., Breitburd F., Croissant O., Jablonska S., Obalek S., Jarzabek-Chorzelska M., Rzesa G. 1980; Epidermodysplasia verruciformis: a model for the role of papillomaviruses in human cancer. In Viruses in Naturally Occurring Cancers vol 7 pp  259–282 Edited by Essex M., Todaro G, zur Hausen H. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
    [Google Scholar]
  17. Salmon J., Ramoz N., Cassonnet P., Orth G., Breitburd F. 1997; A cottontail rabbit papillomavirus strain (CRPVb) with strikingly divergent E6 and E7 oncoproteins: an insight in the evolution of papillomaviruses. Virology 235:228–234 [CrossRef]
    [Google Scholar]
  18. Salmon J., Nonnenmacher M., Cazé S., Flamant P., Croissant O., Orth G., Breitburd F. 2000; Variation in the nucleotide sequence of cottontail rabbit papillomavirus a and b subtypes affects wart regression and malignant transformation and level of viral replication in domestic rabbits. J Virol 74:10766–10777 [CrossRef]
    [Google Scholar]
  19. Shah A. K., Brundage R. C., Gratwohl A., Sawchuk R. J. 1992; Pharmacokinetic model for subcutaneous absorption of cyclosporine in the rabbit during chronic treatment. J Pharm Sci 81:491–495 [CrossRef]
    [Google Scholar]
  20. Sundaram P., Tigelaar R. E., Xiao W., Brandsma J. L. 1998; Intracutaneous vaccination of rabbits with the E6 gene of cottontail rabbit papillomavirus provides partial protection against virus challenge. Vaccine 16:613–623 [CrossRef]
    [Google Scholar]
  21. Tieben L. M., Berkhout R. J. M., Smits H. L., Bouwes Bavinck J. N., Vermeer B. J., Bruijn J. A., Van der Woude F. J., ter Schegget J. 1994; Detection of epidermodysplasia verruciformis-like human papillomavirus types in malignant and premalignant skin lesions of renal transplant recipients. Br J Dermatol 131:226–230
    [Google Scholar]
  22. Turazza E., Lapena A., Sprovieri O., Torres C. P., Gurucharri C., Maciel A., Lema B., Grinstein S., Kahn T. 1997; Low-risk human papillomavirus types 6 and 11 associated with carcinomas of the genital and upper aero-digestive tract. Acta Obstet Gynecol Scand 76:271–276
    [Google Scholar]
  23. Walboomers J. M. M., Jacobs M. V., Manos M. M. 7 other authors 1999; Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 189:12–19 [CrossRef]
    [Google Scholar]
  24. Won Y.-H., Sauder D. N., McKenzie R. C. 1994; Cyclosporin A inhibits keratinocyte cytokine gene expression. Br J Dermatol 130:312–319 [CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.80448-0
Loading
/content/journal/jgv/10.1099/vir.0.80448-0
Loading

Data & Media loading...

Most cited Most Cited RSS feed