Histopathologic and molecular characterization of Erethizon dorsatum papillomavirus 1 and Erethizon dorsatum papillomavirus 2 infection in North American porcupines (Erethizon dorsatum).

Erethizon dorsatum papillomavirus 1 (EdPV1) and Erethizon dorsatum papillomavirus 2 (EdPV2) are associated with cutaneous papillomas in North American porcupines (Erethizon dorsatum). This study defined gross, histopathologic, and molecular characteristics of viral papillomas in 10 North American porcupines submitted to the New York State Animal Health Diagnostic Center. Investigation for the presence of EdPV1 and EdPV2 DNA via polymerase chain reaction (PCR) was performed in 9 of the 10 (90.0%) porcupines, and all porcupines were investigated for the detection and localization of EdPV1 and EdPV2 E6 and E7 nucleic acid via chromogenic in situ hybridization (CISH). Next-generation sequencing (NGS) was performed in 2 porcupines. Papillomas were diagnosed on the muzzle (n = 4), caudal dorsum (n = 1), upper lip (n = 1), chin (n = 1), gingiva (n = 2), and nasal planum (n = 1). Histologically, the lesions consisted of hyperplastic epidermis or epithelium with orthokeratotic keratin, prominent keratohyalin granules, and intranuclear inclusion bodies. PCR identified EdPV1 in 6 of 9 samples and EdPV2 in the remaining 3 samples. NGS resulted in 100% genome coverage of EdPV1 and 76.20% genome coverage of EdPV2 compared with GenBank reference sequences, with 99.8% sequence identity to the complete EdPV2 L1 gene of a novel subtype recently identified in France. Hybridization patterns in 9 of the 10 (90.0%) porcupines were characterized by strong nuclear signals in the superficial epidermis, with strong nuclear and punctate cytoplasmic signals in the stratum spinosum and basale. In one animal, CISH suggested dual EdPV1 and EdPV2 infection.

Treatment of Recurrent Multifocal Cutaneous Squamous Cell Carcinoma in an African Grey Parrot (Psittacus erithacus) with Intralesional Carboplatin in Poloxamer 407.

A 16-year-old male Congo African grey parrot (Psittacus erithacus) was presented with an ulcerated wing mass that was excised and diagnosed on histopathology as squamous cell carcinoma (SCC). A second surgery was performed to completely excise the tumor margins, resulting in over 5 years of remission for the neoplasm. However, over the next 6 years the patient developed SCC in 3 new locations on the body, as well as 2 squamous papillomas. The 2 papillomas were surgically excised and did not recur. Due to their size and location, none of the 3 new SCCs were amenable to complete excision. Instead, the 3 SCCs were managed with a series of treatments with intralesional carboplatin in poloxamer 407 and carbon dioxide surgical laser debridements. This treatment regimen has resulted in long-term (52 months, 30 months, and 17 months) resolution for all 3 of the SCCs. The overall survival time for the patient, from the initial diagnosis to the time of this report, is over 2900 days. While being treated for the 3 SCCs, the African grey parrot had no overt signs of complications or adverse side effects.

Malignant Transformation of a Canine Papillomavirus Type 1-Induced Persistent Oral Papilloma in a 3-Year-Old Dog.

This case report describes a rare case of a persistent canine papillomavirus type 1 (CPV-1)-induced oral papilloma that underwent malignant transformation into an oral squamous cell carcinoma (OSCC) in a 3-year-old Labrador retriever cross. Initially, the patient had multiple and multifocal verrucous lesions populating the oral cavity exclusively. The papillomas persisted despite multiple surgical ablations, azithromycin, interferon α-2b, alternative medicines, and off-label drug use of an immunostimulant. After 1 year and 6 months, an aggressive lesion developed at the level of the left mandibular first molar (309) and progressed to a well-differentiated invasive OSCC. The presence of CPV-1 DNA in the OSCC, and the known oncogenic abilities of CPV-1, suggests that this virus might have played a significant role in the emergence of the OSCC that ultimately led to the patient's euthanasia due to poor quality of life. This is the first well-documented case where OSCC has developed from an oral papilloma caused by CPV-1 in which the presence of coinfection by another papillomavirus was excluded by multiple polymerase chain reaction tests using various primers.

Detection of a Novel Alphaherpesvirus and Avihepadnavirus in a Plantar Papilloma from a Rainbow Lorikeet (Trichoglosis moluccanus).

Cutaneous plantar papillomas are a relatively common lesion of wild psittacine birds in Australia. Next-generation sequencing technology was used to investigate the potential aetiologic agent(s) for a plantar cutaneous papilloma in a wild rainbow lorikeet (Trichoglosis moluccanus). In the DNA from this lesion, two novel viral sequences were detected. The first was the partial sequence of a herpesvirus with the proposed name, psittacid alphaherpesvirus 6, from the Mardivirus genus of the family alphaherpesviruses. This represents the first mardivirus to be detected in a psittacine bird, the first mardivirus to be detected in a wild bird in Australia, and the second mardivirus to be found in a biopsy of an avian cutaneous papilloma. The second virus sequence was a complete sequence of a hepadnavirus, proposed as parrot hepatitis B genotype H (PHBV-H). PHBV-H is the first hepadnavirus to be detected in a wild psittacine bird in Australia. Whether other similar viruses are circulating in wild birds in Australia and whether either of these viruses play a role in the development of the plantar papilloma will require testing of biopsies from similar lesions and normal skin from other wild psittacine birds.

Characterization of the complete genomes of Camelus dromedarius papillomavirus types 1 and 2.

Camel papillomatosis has been described previously, but the genome of the suspected papillomavirus (PV) has not been identified. An outbreak of papillomatosis occurred in a dromedary farm of 55 animals in Sudan during August 2009. The disease was only present in young animals aged about 3-7 months, of which 44 % (11/25) were affected with lesions, mainly on the lips and lower jaw. This study reports for the first time the complete genomes of Camelus dromedarius papillomavirus types 1 (CdPV1) and 2 (CdPV2), isolated from a cauliflower-like nodule and a round oval raised nodule, respectively. Pairwise comparisons of their L1 nucleotide sequences revealed 69.2 % identity, and phylogenetic analyses suggested that these two PV types are grouped within the genus Deltapapillomavirus. Both viruses were isolated from fibropapillomas, although no putative E5 proteins homologous to that of bovine papillomavirus type 1 were identified. The genetic information will be useful for evolutionary studies of the family Papillomaviridae, as well as for the development of diagnostic methods for surveillance of the disease in dromedaries.

Oral fibropapillomatosis and epidermal hyperplasia of the lip in newborn lambs associated with bovine Deltapapillomavirus.

Congenital fibropapillomatosis of the gingiva and oral mucosa and epidermal hyperplasia of the lip are described, for the first time, in two newborn lambs. Expression of the E5 oncoprotein of bovine deltapapillomavirus types 2 (BPV-2) and -13 (BPV-13) was detected in both fibropapillomas and the hyperplastic epidermal cells suggesting the BPV infection was the cause of the proliferative lesions. No DNA sequences of BPV-1 and BPV-14 were detected. Both BPV-2 and BPV-13 DNA were also amplified from peripheral blood mononuclear cells (PBMCs) of the newborn lambs' dams. The concordance between BPV genotypes detected in the blood of dam and the oral and skin pathological samples of their offspring suggests that a vertical hematogeneous transmission was most likely source of BPV infection. Immunoblotting revealed the presence of E5 dimers allowing the viral protein to be biologically active. E5 dimers bind and activate the platelet derived growth factor ß receptor (PDGFßR), a major molecular mechanism contributing to disease. The detection of E5 protein within the proliferating cells therefore adds further evidence that the BPV infection was the cause of the proliferative lesions seen in these lambs. This is the first evidence of vertical transmission of BPVs in sheep resulting in a clinical disease.

Extensive papillomatosis of the bovine upper gastrointestinal tract.

Extensive papillomatosis was identified in a heifer born and raised in Scotland and a steer born and raised in England. In both cases, the papillomas extended from the mouth and tongue to the reticulum. Although cases of florid papillomatosis of the upper gastrointestinal tract occur relatively frequently in cattle grazing on bracken fern in the Scottish Highlands, no such cases have been reported previously in English cattle. Histopathological examination of the papillomas showed that the lesions were wholly epithelial, with acanthosis, hyperkeratosis and the pathognomonic koilocytes characteristic of papillomavirus infection. Bovine papillomavirus type 4 (BPV-4) was identified by molecular amplification and sequencing of the viral genome.

Pigmented chin papillomas in red (Cervus elaphus) x wapiti (Cervus canadensis) stags associated with a novel papillomavirus.

CASE HISTORY: Lesions were observed on the chins of two 2- to 3-year-old red (Cervus elaphus) x wapiti (Cervus canadensis) stags from the lower North Island of New Zealand during velvet removal. CLINICAL FINDINGS: Both stags had numerous, coalescing, darkly pigmented plaques and nodules on the skin of the chin and lower lips that were 3-10 mm in diameter. Re-examination after 12 months of initial detection revealed no appreciable change in the lesions. A biopsy sample from one lesion was submitted for histopathological examination. HISTOPATHOLOGY: Sections revealed lesions consistent with pigmented viral papillomas, characterised by marked epidermal hyperplasia forming papillary fronds, prominent clumping of keratohyalin granules, keratinocytes with dilated grey-blue cytoplasm, shrunken nuclei surrounded by a clear halo (koilocytes), and presumptive viral intranuclear inclusions. Papillomavirus DNA was amplified by PCR from a fresh tissue sample from the same papilloma. Comparison of the partial nucleotide sequence amplified to previously reported papillomaviruses suggested the presence of a novel papillomavirus type. DIAGNOSIS: A presumptive diagnosis of pigmented viral papilloma was made. CLINICAL RELEVANCE: While the papillomas described in these two cases do not appear to cause major clinical disease, they are visually unappealing and have the potential to spread to other valuable deer.

Cottontail rabbit papillomavirus infection in a desert cottontail (Sylvilagus audubonii) from Colorado, USA.

A wild-caught desert cottontail rabbit (Sylvilagus audubonii) from Colorado was observed to have large, pedunculated, dark cutaneous lesions on its abdomen and cylindrical masses on its mouth. Morphologically, the masses were consistent with previous reports of virally induced papillomas. Subsequent DNA analysis indicated widespread infection with cottontail rabbit papillomavirus.

Pathological manifestations of feline immunodeficiency virus (FIV) infection in wild African lions.

Feline immunodeficiency virus (FIV) causes AIDS in the domestic cat (Felis catus) but has not been explicitly associated with AIDS pathology in any of the eight free-ranging species of Felidae that are endemic with circulating FIV strains. African lion (Panthera leo) populations are infected with lion-specific FIV strains (FIVple), yet there remains uncertainty about the degree to which FIV infection impacts their health. Reported CD4+ T-lymphocyte depletion in FIVple-infected lions and anecdotal reports of lion morbidity associated with FIV seroprevalence emphasize the concern as to whether FIVple is innocuous or pathogenic. Here we monitored clinical, biochemical, histological and serological parameters among FIVple-positive (N=47) as compared to FIVple-negative (N=17) lions anesthetized and sampled on multiple occasions between 1999 and 2006 in Botswana. Relative to uninfected lions, FIVple-infected lions displayed a significant elevation in the prevalence of AIDS-defining conditions: lymphadenopathy, gingivitis, tongue papillomas, dehydration, and poor coat condition, as well as displaying abnormal red blood cell parameters, depressed serum albumin, and elevated liver enzymes and gamma globulin. Spleen and lymph node biopsies from free-ranging FIVple-infected lions (N=9) revealed evidence of lymphoid depletion, the hallmark pathology documented in immunodeficiency virus infections of humans (HIV-1), macaques, and domestic cats. We conclude that over time FIVple infections in free-ranging lions can lead to adverse clinical, immunological, and pathological outcomes in some individuals that parallel sequelae caused by lentivirus infection in humans (HIV), Asian macaques (SIV) and domestic cats (FIVfca).

Naturally occurring orocutaneous papillomas and carcinomas of brown bullheads (Ictalurus nebulosus) in New York State.

Ninety-four brown bullheads (Ictalurus nebulosus) with spontaneous orocutaneous neoplasms (papillomas and carcinomas) were studied grossly and by light microscopy. Of these 94 fish, 71 were selected from 505 fish examined macroscopically during field surveys and 23 were selected from those submitted for diagnostic study. Fish with neoplasms came from 17 locations throughout New York State: Buffalo River, Canaan Lake, Cazenovia Lake, Delta Lake, Fort Pond, Greenwood Lake, Hudson River, Lake George, Lake Tiorati, Lincoln Hall Pond. Lincoln Pond, Oneida Lake, Onondaga Lake, Rutland Pond, Salmon River, Silver Stream Reservoir and Swan Lake. The prevalence varied from 0 to 100%. Multiple neoplasms were more common (84/94, 89%) than solitary ones (10/94, 11%). In order of decreasing frequency, neoplasms arose on the head, especially the ventral aspect, the lower dental plate, the upper dental plate, the trunk, the barbels, the fins, the tongue, and the tail. Of the 38/94 brown bullheads (40%) with tumors in both upper and lower lips and dental plates, 24/38 (63%) had the tumors in opposition. Macroscopically, soft, pink or yellowish papillary masses protruded above the normal epithelial surfaces. Histologically, cutaneous and oral neoplasms originated from the morphologically similar Malpighian epithelial cells of the surface epithelia and from the outer cells of the enamel organ. Based on histopathologic criteria, cutaneous and oral neoplasms were considered the same disease in different anatomic locations. No apparent difference in biologic behavior was noted between cutaneous and oral neoplasms. The lesions apparently progressed from benign papilloma to locally invasive carcinoma (28/94, 30%). Neoplastic emboli were seen in one case, and no metastases were detected. There was no statistically significant difference between the susceptibility of males (20/57, 35%) and females (6/26, 23%) to carcinomas. An apparent correlation was noted between a higher frequency of malignant tumors and longer body size (3/13 fish [23%] < 30 cm, 17/54 fish [31%] 30-34 cm, and 7/18 fish [39%] > 34 cm).

The epithelial neoplasm observed in the cultured coho salmon, Oncorhynchus kisutch.

The epithelial neoplasms were observed on the mouth of the cultured coho salmon, Oncorhynchus kisutch. Histopathologically, the tumors were formed to be proliferative epithelial cells, but no change was observed in other organs. The virus from this tumor was isolated in RTG-2 and CHSE-214 cells and developed the cytopathic effect which characterized to be the formation of syncytia and the migration of chromatin. This virus was neutralized with anti-Oncorhynchus masou virus (OMV) rabbit serum.

Excision of tumors in the nasal vestibule of two dogs.

Two dogs with tumors in the left nasal vestibule were treated by surgical excision of the affected part of the nose. Radiation and chemopotentiation were used in one dog, which remained tumor-free after 12 months. When recovering from anesthesia, the second dog developed respiratory distress associated with upper airway obstruction and failure to mouth breathe. The dog was successfully treated by temporary tracheostomy and remained tumor-free after 3 months. Surgery preserved the function of the right nostril and gave an acceptable cosmetic result in both cases.