Canine Papillomavirus—A Centenary Review

Nicholls, P.K.; Stanley, Margaret

doi:10.1053/jcpa.1998.0278

Cited by 55 publications

(48 citation statements)

References 64 publications

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“…To determine whether these in vitro activities were applicable in vivo, we employed the canine oral papillomavirus model. This animal model has been used for evaluating the efficacy of papillomavirus vaccines and has several features which make it an ideal model for mimicking human mucosal papillomavirus infections, both oral and genital (30). One important advantage of this model is that 100% of challenged animals become infected and develop tumors.…”

Section: Resultsmentioning

confidence: 99%

Dihydroartemisinin Is Cytotoxic to Papillomavirus-Expressing Epithelial Cells In vitro and In vivo

et al. 2005

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Nearly all cervical cancers are etiologically attributable to human papillomavirus (HPV) infection and pharmaceutical treatments targeting HPV-infected cells would be of great medical benefit. Because many neoplastic cells (including cervical cancer cells) overexpress the transferrin receptor to increase their iron uptake, we hypothesized that irondependent, antimalarial drugs such as artemisinin might prove useful in treating HPV-infected or transformed cells. We tested three different artemisinin compounds and found that dihydroartemisinin (DHA) and artesunate displayed strong cytotoxic effects on HPV-immortalized and transformed cervical cells in vitro with little effect on normal cervical epithelial cells. DHA-induced cell death involved activation of the mitochondrial caspase pathway with resultant apoptosis. Apoptosis was p53 independent and was not the consequence of drug-induced reductions in viral oncogene expression. Due to its selective cytotoxicity, hydrophobicity, and known ability to penetrate epithelial surfaces, we postulated that DHA might be useful for the topical treatment of mucosal papillomavirus lesions. To test this hypothesis, we applied DHA to the oral mucosa of dogs that had been challenged with the canine oral papillomavirus. Although applied only intermittently, DHA strongly inhibited viral-induced tumor formation. Interestingly, the DHA-treated, tumor-negative dogs developed antibodies against the viral L1 capsid protein, suggesting that DHA had inhibited tumor growth but not early rounds of papillomavirus replication. These findings indicate that DHA and other artemisinin derivatives may be useful for the topical treatment of epithelial papillomavirus lesions, including those that have progressed to the neoplastic state. (Cancer Res 2005; 65(23): 10854-61)

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Section: Resultsmentioning

confidence: 99%

Dihydroartemisinin Is Cytotoxic to Papillomavirus-Expressing Epithelial Cells In vitro and In vivo

et al. 2005

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“…Canine oral papillomas normally occur in young dogs, have a typical exophytic histologic phenotype, and usually spontaneously regress within 4 to 8 weeks (41). Cutaneous papillomas occur uncommonly in the dog and are caused by a papillomavirus that differs from COPV, suggesting at least a second type of canine papillomavirus (12,33,49,52).…”

Section: Discussionmentioning

confidence: 99%

Severe Papillomavirus Infection Progressing to Metastatic Squamous Cell Carcinoma in Bone Marrow-Transplanted X-Linked SCID Dogs

Goldschmidt¹,

Kennedy

et al. 2006

J Virol

115

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Canine X-linked severe combined immunodeficiency (XSCID) is due to mutations in the common gamma chain (␥c) gene and is identical clinically and immunologically to human XSCID, making it a true homologue of the human disease. Bone marrow-transplanted (BMT) XSCID dogs not only engraft donor T cells and reconstitute normal T-cell function but, in contrast to the majority of transplanted human XSCID patients, also engraft donor B cells and reconstitute normal humoral immune function. Shortly after our initial report of successful BMT of XSCID dogs, it soon became evident that transplanted XSCID dogs developed late-onset severe chronic cutaneous infections containing a newly described canine papillomavirus. This is analogous to the late-onset cutaneous papillomavirus infection recently described for human XSCID patients following BMT. Of 24 transplanted XSCID dogs followed for at least 1 year post-BMT, 71% developed chronic canine papillomavirus infection. Six of the transplanted dogs that developed cutaneous papillomas were maintained for >3 1/2 years post-BMT for use as breeders. Four of these six dogs (67%) developed invasive squamous cell carcinoma (SCC), with three of the dogs (75%) eventually developing metastatic SCC, an extremely rare consequence of SCC in the dog. This finding raises the question of whether SCC will develop in transplanted human XSCID patients later in life. Canine XSCID therefore provides an ideal animal model with which to study the role of the ␥c-dependent signaling pathway in the response to papillomavirus infections and the progression of these viral infections to metastatic SCC.Severe combined immunodeficiency (SCID) is a heterogeneous group of diseases characterized by the inability to mount humoral and cell-mediated immune responses, and it is invariably fatal within the first 2 years of life (9, 46). X-linked SCID (XSCID) is the most common form of the disease, representing approximately 50% of all human SCID cases (9, 18). XSCID is caused by mutations in the common gamma (␥c) subunit of the receptors for interleukin-2 (IL-2), IL-4, IL-7, IL-9, IL-15, and IL-21 (reviewed in references 4 and 34). Thus, the XSCID phenotype is the complex result of multiple cytokine defects. The shared usage of the ␥c subunit by receptors for growth factors that are critical for normal B-, NK-, and T-cell development and function explains the profound immunologic abnormalities and clinical severity of the disease.Since the first successful HLA-identical bone marrow transplant in a boy with SCID in 1968 (19), bone marrow transplantation (BMT) has become the treatment of choice for all forms of SCID (10,18,22). SCID patients receiving a histocompatible (HLA-identical) BMT have Ͼ90% long-term survival rates (10,18,22). However, the majority of patients do not have a histocompatible donor. Haploidentical (half-matched) BMT with T-cell depletion to prevent fatal graft-versus-host disease has become the standard therapy for SCID patients who lack a histocompatible donor (10,18,22). Although T-cell depletion...

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“…1,2,6,12 Canine oral papillomavirus (COPV) is classified as lambdapapillomavirus and associated with papillomas, or warts, in the oral cavity of both domestic dogs and wild canids. 12 After an incubation period of 1 or 2 months, the benign lesions usually do not elicit any serious problems, and even severe oral papillomatosis shows spontaneous immune-mediated regression. However, some cases are refractory to treatment, 11 and, rarely, squamous cell carcinomas of the skin and gingiva have also been associated with canine papillomavirus infections.…”

mentioning

confidence: 99%

Detection of Canine Oral Papillomavirus DNA in Conjunctival Epithelial Hyperplastic Lesions of Three Dogs

Brandes

Fritsche²,

Mueller³

et al. 2009

Vet Pathol

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Abstract. Papillomavirus infections are responsible for plaques and papillomas in various locations on the skin and in mucous membranes. The aim of this report was to describe morphologic features of a viral pigmented conjunctival plaque and 2 conjunctival squamous papillomas in 3 dogs, and to investigate these lesions for the presence of papillomavirus DNA by polymerase chain reaction (PCR), DNA sequence analysis, and in situ hydridization (ISH). Histopathology revealed in all neoplasms various degrees of epithelial hyperplasia, acanthosis, and hyperkeratosis with koilocytosis. In all lesions E6, E7, and L1 gene fragments of canine oral papillomavirus (COPV) DNA were detected by PCR and sequencing analysis. ISH revealed COPV DNA in a highly specific pattern within nuclei of the hyperplastic epithelium. The presence of canine papillomavirus in ocular conjunctival plaques and papillomas suggests these benign lesions may have the potential for malignant transformation. This is the first time that the lambdapapillomavirus COPV has been detected in ocular epithelial hyperplastic lesions.

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Canine Papillomavirus—A Centenary Review

Cited by 55 publications

References 64 publications

Dihydroartemisinin Is Cytotoxic to Papillomavirus-Expressing Epithelial Cells In vitro and In vivo

Dihydroartemisinin Is Cytotoxic to Papillomavirus-Expressing Epithelial Cells In vitro and In vivo

Severe Papillomavirus Infection Progressing to Metastatic Squamous Cell Carcinoma in Bone Marrow-Transplanted X-Linked SCID Dogs

Detection of Canine Oral Papillomavirus DNA in Conjunctival Epithelial Hyperplastic Lesions of Three Dogs

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