Large cutaneous rabbit papillomas that persist during cyclosporin A treatment can regress spontaneously after cessation of immunosuppression.
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.
Hu
Jiafen
J
Department of Pathology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.|The Jake Gittlen Cancer Research Institute, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
Peng
Xuwen
X
Department of Comparative Medicine, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
Cladel
Nancy M
NM
Department of Pathology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.|The Jake Gittlen Cancer Research Institute, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
Pickel
Martin D
MD
Department of Pathology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.|The Jake Gittlen Cancer Research Institute, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
Christensen
Neil D
ND
Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.|Department of Pathology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.|The Jake Gittlen Cancer Research Institute, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
D000595:Amino Acid Sequence; D000818:Animals; D017849:Animals, Inbred Strains; D021461:Animals, Outbred Strains; D001835:Body Weight / Q000187:drug effects; D016516:CD4-CD8 Ratio; D012777:Cottontail rabbit papillomavirus / Q000235:genetics / Q000472:pathogenicity; D016572:Cyclosporine / Q000494:pharmacology*; D004195:Disease Models, Animal; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009154:Mutation; D009365:Neoplasm Regression, Spontaneous / Q000276:immunology*; D009856:Oncogene Proteins, Viral / Q000235:genetics; D010212:Papilloma / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D010957:Plasmids; D011817:Rabbits; D012878:Skin Neoplasms / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D013997:Time Factors
C469554:E6 protein, Cottontail rabbit papillomavirus; D007166:Immunosuppressive Agents; D009856:Oncogene Proteins, Viral; D016572:Cyclosporine