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The objective of this cross-sectional study was to assess the prevalence and risk factors for teat warts, udder edema, udder thigh dermatitis, and udder cleft dermatitis on Bavarian dairy farms. Udder health and hygiene scores of lactating cows were recorded on 152 farms in Bavaria, Germany. Management practices (e.g., housing, milking systems, and feeding regimens) were assessed with a comprehensive questionnaire. Adjusted prevalence estimates were determined using regression analysis with herd as the random effect. Mann-Whitney U or Fisher's exact on herd level and regression analyses on cow level were performed to determine risk factors. Of the 6,208 cows examined, 4.0% had teat warts, 1.1% udder edema, 0.2% udder thigh dermatitis, and 0.3% udder cleft dermatitis. The apparent median within-herd prevalence was less than 4% for all 4 diseases. Herd-level factors that were associated with the presence of teat warts on a farm were the proportion of cows with poor teat ends as well as conventional milking systems compared with milking robots. At a cow level, teat warts were associated with high somatic cell counts. Herds with poor depth (<5 cm) of bedding material and cows with days in milk less than 60 d had increased odds for udder edema. First-lactating cows had higher odds for udder thigh dermatitis. Freestall housing and comfort rubber mats were identified as risk factors for udder cleft dermatitis on a herd level. In conclusion, although most nonmastitis udder diseases were rarely observed in this study, some herd management practices and cow factors were associated with their presence on a farm or cow level. Future studies are needed to further investigate risk factors for each disease in more detail., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Pathogen-induced cancers account for 15% of human tumors and are a growing concern for endangered wildlife. Fibropapillomatosis is an expanding virally and environmentally co-induced sea turtle tumor epizootic. Chelonid herpesvirus 5 (ChHV5) is implicated as a causative virus, but its transmission method and specific role in oncogenesis and progression is unclear. We applied environmental (e)DNA-based viral monitoring to assess viral shedding as a direct means of transmission, and the relationship between tumor burden, surgical resection and ChHV5 shedding. To elucidate the abundance and transcriptional status of ChHV5 across early, established, regrowth and internal tumors we conducted genomics and transcriptomics. We determined that ChHV5 is shed into the water column, representing a likely transmission route, and revealed novel temporal shedding dynamics and tumor burden correlations. ChHV5 was more abundant in the water column than in marine leeches. We also revealed that ChHV5 is latent in fibropapillomatosis, including early stage, regrowth and internal tumors; higher viral transcription is not indicative of poor patient outcome, and high ChHV5 loads predominantly arise from latent virus. These results expand our knowledge of the cellular and shedding dynamics of ChHV5 and can provide insights into temporal transmission dynamics and viral oncogenesis not readily investigable in tumors of terrestrial species.

Currently, bovine papillomavirus types are divided into five genera, namely, Deltapapillomavirus, Epsilonpapillomavirus, Xipapillomavirus, Dyoxipapillomavirus, and Dyokappapapillomavirus. In the recent decades, the characterization of numerous putative and novel bovine papillomavirus types from cattle in several geographic regions, has revealed the occurrence of a high viral diversity. In this study, we describe the identification and characterization of a putative new bovine papillomavirus type within species Xipapillomavirus 1 of Xipapillomavirus genus. The detection of the viral types identified in the skin warts was obtained by polymerase chain reaction assays targeting the L1 gene, followed by direct sequencing of the generated amplicons. The partial L1 sequences revealed that bovine papillomavirus types 6, 10, and 11, the putative new bovine papillomavirus type designated BPV/CHI-SW2, and an unreported putative new bovine papillomavirus type (named BPV/BR-UEL08) were associated with cutaneous papillomatosis in the cows from the dairy herd investigated. Phylogenetic reconstruction based on the L1 gene revealed that the BPV/BR-UEL08 isolate clustered with other bovine papillomaviruses classified in the Xipapillomavirus genus, being closely related to representatives of the species Xipapillomavirus 1. Investigations focusing on the molecular epidemiology of bovine papillomaviruses related to clinical outcomes in cattle are of fundamental importance to determine the actual genetic diversity and prevalent viral types to be included in vaccines for cattle.

Background: Canine papillomavirus (CPV) has 20 described types associated with papillomas or squamous cell carcinoma (SCC). Knowledge about CPV diversity is scarce. Studies on papillomaviruses that infect other hosts show substantial diversity with some types and variants being associated with cancer., Hypothesis/objectives: The aim of this study was to assess the genetic variability of the capsid L1 gene of CPV identified in lesions of naturally infected dogs from Brazil., Animals: Six dogs presenting with oral and cutaneous warts from different veterinary clinics in Sergipe state, Northeast Brazil., Methods and Materials: Nine skin biopsy samples were collected for histopathological and molecular analyses. Bioinformatics tools were used for genotyping and diversity analysis. Mutations were characterized based on their impact on the L1 protein structure., Results: Sequences of CPV1 were obtained from exophytic papillomas. These sequences had at least five different mutations showing that all sequences were putative CPV1 variants. One CPV1 sequence, obtained from an oral SCC, had a highly destabilizing substitution in the L1 protein which was likely to be associated with changes in protein function., Conclusions and Clinical Importance: Despite the small number of cases analysed and the partial analysis of L1 nucleotide and amino acid sequences, this study has demonstrated diversity in CPV samples from Northeast Brazil. A putative new CPV1 variant associated with oral SCC, with novel protein structure changing mutations, was identified which may be important for understanding papillomavirus pathogenesis., (© 2019 ESVD and ACVD.)

Cases of wart-like lesions in humans and dromedary camels occurred in eastern Sudan in 2015 were described. Involvement of papillomavirus (PV) in causing these cases was affirmed by PCR and immunoperoxidase test. Mostly, the lesions were observed on the skin of the chest and forearms in addition to lips and mandible. Sequence analysis revealed Camelus dromedarius PV types 1 and 2 genotypes as the causative genotypes. We also observed cases of wart-like lesions on hands and legs of two herders attending the infected camel herd. Partial genome sequencing revealed human PV type 2 in one of the two human samples providing no indications for interspecies transmission of camel PVs, yet provides, for the first time evidence of active circulation of this virus in eastern Sudan.

This study diagnosed cutaneous wart lesions excised from three rams from a sheep farm in São Paulo State, Brazil. Histopathologically, these cases were diagnosed as papilloma. The amplification by PCR, sequencing and bioinformatics analysis showed that all the lesions presented DNA sequences of bovine papillomavirus type 2. This is the first report confirming the detection of BPV2 in papilloma warts from ovines., (© 2018 Blackwell Verlag GmbH.)

Mouse papillomavirus type 1 (MmuPV1) provides, for the first time, the opportunity to study infection and pathogenesis of papillomaviruses in the context of laboratory mice. In this report, we define the transcriptome of MmuPV1 genome present in papillomas arising in experimentally infected mice using a combination of RNA-seq, PacBio Iso-seq, 5' RACE, 3' RACE, primer-walking RT-PCR, RNase protection, Northern blot and in situ hybridization analyses. We demonstrate that the MmuPV1 genome is transcribed unidirectionally from five major promoters (P) or transcription start sites (TSS) and polyadenylates its transcripts at two major polyadenylation (pA) sites. We designate the P7503, P360 and P859 as "early" promoters because they give rise to transcripts mostly utilizing the polyadenylation signal at nt 3844 and therefore can only encode early genes, and P7107 and P533 as "late" promoters because they give rise to transcripts utilizing polyadenylation signals at either nt 3844 or nt 7047, the latter being able to encode late, capsid proteins. MmuPV1 genome contains five splice donor sites and three acceptor sites that produce thirty-six RNA isoforms deduced to express seven predicted early gene products (E6, E7, E1, E1^M1, E1^M2, E2 and E8^E2) and three predicted late gene products (E1^E4, L2 and L1). The majority of the viral early transcripts are spliced once from nt 757 to 3139, while viral late transcripts, which are predicted to encode L1, are spliced twice, first from nt 7243 to either nt 3139 (P7107) or nt 757 to 3139 (P533) and second from nt 3431 to nt 5372. Thirteen of these viral transcripts were detectable by Northern blot analysis, with the P533-derived late E1^E4 transcripts being the most abundant. The late transcripts could be detected in highly differentiated keratinocytes of MmuPV1-infected tissues as early as ten days after MmuPV1 inoculation and correlated with detection of L1 protein and viral DNA amplification. In mature warts, detection of L1 was also found in more poorly differentiated cells, as previously reported. Subclinical infections were also observed. The comprehensive transcription map of MmuPV1 generated in this study provides further evidence that MmuPV1 is similar to high-risk cutaneous beta human papillomaviruses. The knowledge revealed will facilitate the use of MmuPV1 as an animal virus model for understanding of human papillomavirus gene expression, pathogenesis and immunology.

Papillomas occur more frequently in cattle than other domestic animals. The causal agent of bovine papillomatosis is a virus that belongs to the family Papillomaviridae. In Tamaulipas, Mexico, the virus is considered a serious problem and has impeded the export of cattle to the United States, resulting in serious economic losses. Owing to the lack of information regarding the subtypes of papillomaviruses that infect cattle in Mexico, the aim of this study was to determine the subtypes in Tamaulipas. Fifty-two warts were analyzed with the use of polymerase chain reaction (PCR) involving primers that amplify the E7 gene of bovine papillomavirus (BPV). The PCR products were sequenced to differentiate the BPV-1 and BPV-2 subtypes. The sequencing quality was determined with the use of MEGA 6.0 software. Comparison of the Tamaulipas sequences with those of known BPV types by means of the MUSCLE algorithm showed that 53% of the former were BPV-1 and 47% were BPV-2. The distribution of the 2 subtypes in the cattle was homogeneous. This study demonstrated the presence of BPV-1 and BPV-2 in cattle from Tamaulipas and constitutes the first molecular characterization of papillomas in Mexico.

Teat papillomatosis affects dairy cows worldwide. Milking can become difficult due to teat warts, and maintaining affected cows in the herds may diminish economic profit in the dairy industry. Currently, 13 bovine papillomavirus (BPV) types have been fully characterized, and numerous putative BPV types have been identified through partial L1 gene PCR. In order to identify the viral types present in warts on the udders of dairy cows, 40 teat lesions from 24 cows from 13 cattle farms in three States of Brazil were evaluated by PV L1 gene PCR. The warts that were evaluated contained sequences from BPVs 6-10, the putative BPV types BAPV9 and BAPV4, and two unreported putative papillomavirus (PV) types, named BPV/BR-UEL6 and BPV/BR-UEL7. In addition, mixed infections and coinfections were identified, since more than one lesion was observed on the udders of 13 cows. Phylogenetic analysis showed that BPV/BR-UEL6 is closely related to BPVs belonging to the genus Xipapillomavirus, while BPV/BR-UEL7 clustered with the previously reported strains Cervus timorensis and Pudu puda PVs, which represent a putative new PV type, and it was only distantly related to xi-, epsilon-, delta- and dyoxi-PVs. These results provide information that will assist in the understanding of the association of BPVs 6, 7, 8, 9, and 10, as well as putative BPV types BAPV4 and BAPV9, with mammary papillomatosis. This is the first characterization of putative novel PV types BPV/BR-UEL6 and BPV/BR-UEL7 in teat warts of dairy cows, highlighting the high genetic diversity of BPVs associated with teat papillomatosis.

Bovine papilloma is a chronic and proliferative skin and mucosal wart caused by Bovine papillomavirus (BPV). In June, 2013, a leaf-and flat-shaped wart disease was observed on the nipple skins in a cattle farm in Xinjiang. To diagnose the disease, we collected the diseased skins for pathological biopsy and DNA analysis by PCR amplification using a pair of degenerate primers FAP59 and FAP64. Sequencing and phylogenetic analysis showed that the infection was caused by a variant of BPV3 and putatively a new subtype of BPV (BPV/CHI-SW1, belonging to the Xi papillomavirus genus). This is the first report of mixed infection caused by variant of BPV3 and BPV (putatively new subtype) in China, and would be of importance for the molecular epidemiological study of the disease., (© 2014 Blackwell Verlag GmbH.)

Papillomaviruses are small and complex viruses that belong to the Papillomaviridae family, which comprises 39 genera. The bovine papillomavirus (BPV) causes an infectious disease that is characterized by chronic and proliferative benign tumors that affect cattle worldwide. Different genotypes of BPVs can cause distinct skin and mucosal lesions and the immunity they raise has low cross-protection. This report aimed to genotype BPVs in cattle from Northern Brazil based on nucleotide partial sequences of the L1 ORF. Skin wart samples from 39 bovines clinically and histopathologically diagnosed as cutaneous papillomatosis from Acre and Rondônia States were analyzed. The results revealed four already reported BPV types (BPVs 1, 2, 11, and 13), nine putative new BPV subtypes and four putative new BPV types as well as two putative new BPV types that were already reported. To our knowledge, this is the first record of BPVs from the Brazilian Amazon region that identified new possible BPV types and subtypes circulating in this population. These findings point to the great genetic diversity of BPVs that are present in this region and highlight the importance of this knowledge before further studies about vaccination are attempted.

In present investigation, etiopathological characterization of upper gastrointestinal tract (GIT) tumours of cattle and buffaloes was undertaken. A total of 27 GIT wart-like lesions in rumen, reticulum, mouth and oesophagus of cattle and buffaloes revealed the presence of small nodular to larger spherical or slender growths with thin base present on mucosa and ruminal pillar. Histopathologically, these cases were diagnosed as fibropapilloma/papilloma. This is the first world record on ruminal papillomatosis in buffaloes. Ruminal warts of cattle and buffaloes revealed the presence of BPV-5, -1 & -2, which is the first report of presence of these BPVs in the ruminal warts from India. Quantitative real-time PCR revealed that DNA samples of different GIT wart-like lesions contained varying amount of BPV DNA copy numbers. Immunohistochemistry revealed that the PCNA and Ki67 immunopositivity was present in the basal and spinosum layer of the fibropapilloma/papilloma, indicating these as the cellular proliferation site. In conclusion, the present investigation revealed that BPV-5, -1 & -2 are associated with certain ruminal wart-like lesions/growths in cattle and buffaloes, and the basal and spinosum layer of the ruminal fibropapilloma/papilloma were cellular proliferation sites., (© 2013 Blackwell Verlag GmbH.)

Seven clinical cases of cutaneous papillomatosis in yaks were studied in Arunachal Pradesh, India. Sporadic, single or a chain of multiple varying size warts appeared around the eyes or on the body. Predominant site of warts was around eyes. Histopathologically, these cases were diagnosed as fibropapilloma. It was confirmed by the detection of BPV-1 and BPV-2 or their mixed infection by PCR and sequencing. Quantitative SYBR Green real-time PCR detected comparatively lower viral DNA copy number in cutaneous warts (CWs). Cases of CWs and its causative agent as bovine papillomavirus (BPVs) are reported for the first time in yaks., (© 2012 Blackwell Verlag GmbH.)

The diversity of papillomavirus (PV) found in bovine cutaneous warts from Brazilian cattle was evaluated using the PCR technique with the utilization of consensus primers MY09/11 and by PCR using Bovine Papillomavirus (BPV) type-specific primers followed by sequencing. Eleven cutaneous warts from 6 cattle herds were selected. Six warts were positive for the presence of PV. The presence of BPV types 1, 2, 3, 6 and feline sarcoid-associated PV (FeSarPV) in cutaneous wart lesions, as well as the presence of co-infections, was found. To the best of our knowledge, this is the first time that FeSarPV is described co-infecting a cutaneous wart in Brazil. The present study confirms the previous finding of FeSarPV infecting cattle. These results show the necessity of more studies to investigate the diversity of PV in cattle, its diversity and the possibility of co-infection in cattle and other animals., (© 2012 Blackwell Verlag GmbH.)

Viral cutaneous lesions are frequent in some bird populations, though we are generally ignorant of the causal agent. In some instances, they represent a threat to livestock and wildlife health. We present here a multiplex PCR which detects and distinguishes infection by two such agents, avipoxviruses and papillomaviruses, in avian hosts. We assayed biopsies and superficial skin swabs from field and preserved museum skin specimens. Ninety-three percent of samples from symptomatic specimens tested positive for the presence of avipox (n = 23) or papillomavirus (n = 5). Sixteen and five sequences, corresponding to the P4b and L1 genes, were obtained from avipox and papillomavirus, respectively. One museum specimen, of Fringilla coelebs (chaffinch), was apparently infected with both viruses. Although papillomavirus sequences proved identical to previously published sequences, four novel avipox sequences were generated and used to build a neighbor-joining phylogenetic tree. Our tree recovered a similar topology to that of several recent authors; however, we also propose here two new minor avipox clades (B1b and B3). This multiplex PCR technique shows improved sensitivity compared to other avipox and papillomavirus assays, is able to detect a wide range of avipox and papillomavirus types (it amplifies all three avian-derived papillomavirus genera described thus far and sequences from both major avipox clades), and was even able to detect ancient viral DNA contained in museum specimens of greater than 75 years antiquity for both viruses.

Polymerase chain reaction-based bovine papillomavirus (BPV) detection methods using a combination of two primer sets, subAup/subAdw and subBup/subBdw, have enabled the broad-spectrum detection of most characterized BPV types. These methods were used to detect the partial L1 nucleotide sequence of BPV types from 167 cutaneous warts in cattle. Three potentially new viruses were detected using subBup/subBdw primer sets. The partial nucleotide sequences of these viruses were most similar to BPV-4, -6 and -9. Whole genome sequencing of one sample defines a new BPV type in the genus Xipapillomavirus, designated BPV-11.

Papilloma viruses are detected and identified by PCR with consensus primers designed from human papilloma virus sequences. These and other primers could not detect papilloma virus in bovine teat wart samples despite repeated attempts. DNase-SISPA, a metagenomic method for identifying viruses, could identify bovine papilloma virus type 10 in bovine teat warts. The sequence comparison between consensus primers and bovine papilloma virus type 10 sequences revealed many differences between consensus primers and BPV-10 sequences. We suggest, DNase-SISPA may be used as an alternate method for papilloma virus diagnosis, in cases where PCR fails to identify papilloma viruses., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Bovine papillomaviruses (BPV) induce benign tumours of the cutaneous or mucosal epithelia in cattle, but are also involved in the development of cancer of the urinary bladder and of the upper gastrointestinal tract. Current BPV genotyping assays employ techniques developed originally for the detection of human papillomaviruses. These methods rely on consensus PCR amplification and subsequent sequencing and are cumbersome and limited in their analytic sensitivity to detect BPV, especially in multiple infections. In this study, a novel multiplex BPV genotyping assay is described to detect sensitively and specifically BPV-1 to -10 as well as BaPV-11. The assay is based on a multiplex PCR using novel broad-spectrum bovine papillomavirus (BSBP) primers followed by multiplex bovine genotyping (MBG) by Luminex xMAP technology. The detection limit of the assay was shown to be between 10 and 100 BPV genomes. In a first application, BPV was detected in 100% of wart preparations with BPV-8 being most prevalent, followed by types 6, 1 and 10. The majority of warts were positive for at least four BPV types. In conclusion, BSBP-PCR/MBG is a powerful high-throughput method suitable for the study of the natural history of BPV and could be useful to veterinarians for the monitoring of the efficacy of future BPV vaccines., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Bovine cutaneous warts (CWs) were investigated in Northern India. Of 49 cases, 44 were recorded in cattle and 5 in buffaloes. These animals had mild to moderate grade infections. Grossly, cases of CWs appeared to be of exophytic type, however, different types of growth patterns were observed. A total of 26 biopsies (cattle 21 and buffaloes 5) from CWs-affected animals studied histopathologically were diagnosed as exophytic and cauliflower-like fibropapilloma 13, exophytic and dome-shaped fibropapilloma 5, occult and/or fibroblastic type papilloma 3, cauliflower-like papilloma 3, endophytic fibropapilloma 1 and fibroma 1. On PCR analysis, 11 CWs and 2 normal skin samples showed BPV-1, -2 mixed infections. A rapid, sensitive and reliable real-time SYBR Green PCR test to detect BPV-1, BPV-2 and to quantify BPV-1 was developed. Results of amplification and dissociation plot of real-time PCR revealed that six samples were BPV-1 positive, eight were BPV-2 positive and six were positive for both BPV-1 and -2. CWs samples from different dairy farms testing positive for BPV-1 by PCR assay were also positive using Quantitative real-time SYBR Green PCR assay. For the first time, mixed infection of BPV-1 and -2 was detected in India and BPV-1 load was quantified by real-time SYBR Green PCR assay.

Papillomaviruses have been reported to be very difficult to grow in cell culture. Also, there are no descriptions of cell cultures from lesions of bovine cutaneous papillomatosis, with identification of different bovine papilloma virus (BPV) DNA sequences. In the present report, we describe primary cell cultures from samples of cutaneous lesions (warts). We investigated the simultaneous presence of different BPV DNA sequences, comparing the original lesion to different passages of the cell cultures and to peripheral blood. BPV 1, 2 and 4 DNA sequences were found in lesion samples, and respective cell cultures and peripheral blood, supporting our previous hypothesis of the possible activity of these sequences in different samples and now also showing how they can be maintained in different passages of cell cultures.

The effects of four different intervention strategies on the incidence of severe lesions of digital dermatitis in an experimental dairy herd were compared with the effects of a control strategy consisting of walking the cows twice through a footbath containing 4 per cent formaldehyde on one day a week for 24 weeks. The four alternative strategies were the same treatment every other week; standing for 30 minutes in a footbath containing a 2 per cent multicompound solution on days 0, 7, 28 and 90 after having had their hooves cleaned indirectly with a medium pressure spray of water; walking twice through the multicompound solution on one day a week for 24 weeks; and, walking twice through a footbath containing 3 per cent sodium carbonate on one day a week for 24 weeks. The cows' hooves were inspected every three weeks by one trained claw trimmer who graded the lesions of digital dermatitis. None of the alternative strategies significantly reduced either the number or severity of the lesions in comparison with the control strategy. In the groups treated by the third and fourth strategies there were outbreaks of digital dermatitis in which more than 30 per cent of the cows suffered the most severe type of lesion, and there was a continuously high rate of new infections in the group treated by the fourth strategy.

Objective: To determine whether cyclosporine A-induced hyperplastic skin lesions of dogs were associated with papillomavirus infections., Animals: 9 dogs that were treated with cyclosporine A and developed hyperplastic skin lesions., Procedure: History and clinical and histopathologic data were collected. Paraffin-embedded skin biopsy specimens from hyperplastic skin lesions were immunostained for common papillomavirus genus-specific structural antigens by use of a polyclonal rabbit anti-bovine papillomavirus type 1 antiserum. Sections from each tissue block underwent DNA extraction, and polymerase chain reaction (PCR) assays were performed with several sets of primers to amplify a wide range of papillomavirus DNA from humans and other animals., Results: In 7 of 9 dogs, there were more than 10 hyperplastic skin lesions that microscopically resembled those of psoriasiform lichenoid dermatosis. In those dogs, results of testing for papillomavirus via immunohistochemical analyses and PCR assays were negative. In the other 2 dogs, there were only 1 and 3 verrucous lesions, and in those dogs, histologic evaluation revealed koilocytes and nuclear viral inclusions that were immunoreactive for papillomavirus antigens. Papillomavirus DNA was amplified from both dogs. One of the sequences was characteristic for the canine oral papillomavirus, whereas the other had similarities with the recently described canine papillomavirus 2., Conclusions and Clinical Relevance: In dogs, hyperplastic skin lesions occasionally develop during treatment with cyclosporine A. Most of the lesions resemble those of psoriasiform lichenoid dermatosis, although papillomavirus can be detected in some instances.

In the present field study the skin of the feet of 37 heavy draught horses of different breeds showing verrucous pastern dermatitis was examined clinically. Included were the degree of severity of the disease and the prevalence of anatomically normal structures associated with the skin: fetlock tufts of hair ("feathering"), ergots, chestnuts, bulges in the pastern region, cannon circumference. Each horse was examined for Chorioptes sp. skin mites. Information was also collected on the development of the skin alterations and housing conditions and feeding. These individual data were correlated with the clinical degree of severity of verrucous pastern dermatitis, which was evaluated using a numerical code (scoring system). In addition, punch biopsies were taken from the diseased skin of the feet and from healthy skin of the neck for comparative patho-histological examination (see Part III). Verrucous pastern dermatitis is a chronic disease which can be divided into four groups: scaling (group I), hyperkeratotic and hyperplastic plaque-like lesions (group II), tuberous skin masses (group III), and verrucous skin lesions with rugged surfaces (group IV). No correlation was found between the clinical degree of severity of the skin lesions and sex, breed, amount of work, use of stallions for breeding, grooming condition of the hair, white markings in the foot region, or Chorioptes sp. infestation. In regard to feeding it was found that the amount of maize and oats fed had some influence on the clinical degree of severity. Statistical analysis revealed a significant correlation between the clinical degree of severity and the age, the grooming condition of the hooves, and the mean cannon circumference. The prevalence of fetlock tufts of hair, chestnuts, ergots, and anatomically normal bulges in the pastern region also increased significantly with the clinical degree of severity. Furthermore the study revealed that the clinical degree of severity depended on the hygienic conditions of the stables and of the ground where the horses were kept outdoors.

This report describes the clinical and laboratory findings for 5 sheep from 3 different flocks with extensive proliferative skin lesions grossly resembling warts on the distal limbs. The lesions affected the front and rear extremities in all sheep, and 2 sheep also had lesions around the head. The sheep exhibited signs of pain when the lesions were touched, and most sheep were reluctant to move. Various empirical treatments, including systemic antibiotics, topical antibiotics, and antifungal ointments, were administered without clinical improvement. Diagnostic tests including skin biopsy and histopathology, examination of skin scrapings, bacteriology, mycology, electron microscopy of lesions, and immunohistochemical analysis demonstrated that the lesions were the result of parapoxvirus infection. All 5 animals were euthanized either because of the lack of resolution of clinical signs or a decision by the owner. These animals illustrate an atypical presentation of parapoxvirus infection in sheep (orf, contagious ecthyma, and scabby mouth). The infection appeared to be minimally contagious; however, the lesions did not spontaneously resolve. This appears to be the 1st report of such lesions in multiple sheep in North America, although similar lesions have been reported in Israel and the United Kingdom.

The study was carried out on a single herd of 500 Holstein breed dairy cattle. Only 50 dairy cows (10%) were found to be suffering from focal ulcerative and papillomatous digital dermatitis of the pastern region. The cows were subjected to clinical and histopathological examinations. Early ulcerative stage was seen in 30 cows and late papillomatous stage was observed in 20 cows. The topical application of oxytetracycline solution or benzathine penicillin powder appeared to be effective for the treatment of the ulcerative lesions. The histopathological findings showed signs of epidermopoiesis and papilloma formation. The dermal reaction revealed signs of fibroplasia and perivascular aggregation of inflammatory cells. Silver stained sections indicated the presence of longer filamentous spiral spirochetes, cocci and large-sized anaerobic bacilli invading the stratum spinosum. In conclusion it can be said that bovine digital dermatitis was observed in ulcerative and papillomatous form at the pastern region bordering the dewclaws. Spirochetes are frequently associated with and may be responsible for pathological changes in the lesion.

Papillomaviruses are species- and tissue-specific double-stranded DNA viruses. These viruses cause epithelial tumours in many animals, including man. Typically, the benign warts undergo spontaneous, immune-mediated regression, most likely effected by T-cells (especially CD4, but also CD8 subsets), whereas humoral immunity can prevent new infections. Some papillomavirus infections fail to regress spontaneously and others progress to malignant epithelial tumours. Additionally, the impact of these lesions is greater in immunosuppressed individuals. Many therapies are ineffective, and there is much interest in the potential for immunological intervention in papillomavirus infections of man and animals. Vaccination can be achieved with 'live' virus, formalin-inactivated virus, synthetic virus-like particles, and DNA vaccination. There has been much recent progress in the development of such vaccines for papillomavirus infections in the rabbit, ox and dog. Success in these animal models suggests that similar approaches may prove useful for prophylactic or therapeutic vaccination against the important human papillomaviruses involved in the development of cutaneous and anogenital warts, laryngeal papillomatosis, and cervical cancer.

A previously unknown, cutaneous papillomavirus (Papovaviridae) in a brushtail possum (Trichosurus vulpecula) was demonstrated. This represents one of the first viruses reported in this species. Possum papillomas were identified by typical wart-like appearance and histology. Papillomavirus particles were detected by electron microscopy in tissue homogenates following purification and negative staining. The polymerase chain reaction amplified a conserved portion of the L1 gene which was purified and sequenced. Comparison of the DNA and deduced amino acid sequence from the possum papillomavirus with other papillomavirus sequences, together with phylogenetic analysis, indicated that this was a new papillomavirus.

Papillomaviruses occasionally cause severe, nonregressing or recurrent infections in their human and animal hosts. The mechanisms underlying these atypical infections are not known. Canine oral papillomavirus (COPV) typically regresses spontaneously and is an important model of mucosal human papillomavirus infections. A severe, naturally occurring, nonregressing COPV infection provided an opportunity to investigate some aspects of viral pathogenicity and host immunity. In this case, the papillomas proved refractory to surgical and medical treatments, including autogenous vaccination and vaccination with capsid (L1) virus-like particles. High levels of induced anti-L1 antibodies appeared to have no effect on the infection. The papillomas spread to oesophageal mucosa, perioral haired skin, and remote cutaneous sites. Isolation of COPV from the animal and sequencing of several regions of the viral genome showed no differences to the COPV prototype. Experimental infection of beagle dogs with this viral isolate resulted in the uncomplicated development and regression of oral warts within the usual period, indicating that the virus was not an unusual pathogenic variant. These findings support the hypothesis that the recurrent lesions seen in some human papillomavirus infections, such as recurrent laryngeal papillomatosis, are associated with specific defects in host immunity rather than variations in viral pathogenicity., (Copyright 1999 Academic Press.)

The objective of this study was to describe the incidence of papillomatous digital dermatitis in the US (including regional and herd size patterns) and to evaluate specific herd-level management factors associated with high incidence of digital dermatitis in US dairy herds. The study design was a population-based cross-sectional survey. US dairy operations with at least 30 cows in 20 states, representing 79% of US dairy cows, were sampled. On participant operations, a questionnaire was administered by veterinary medical officer or animal-health technicians on-farm to dairy managers. Papillomatous digital dermatitis was reported in milk cows in the previous 12 months from 43.5% of US dairy herds. Seventy-eight percent of affected herds reported that their first cases occurred in 1993 or later. Regions of the USA with the highest percent of herds affected included the Southwest, Northwest, and Northeast. Factors associated with high (> 5%) incidence of papillomatous digital dermatitis included region, herd size, type of land lactating cows accessed on a daily basis, flooring type where lactating cows walked, percent of cows born off the operation, use of a primary hoof trimmer who trimmed cows' hooves on other operations, and lack of washing of hoof-trimming equipment between cows. Papillomatous digital dermatitis has been recently reported from dairy herds across the US. This study suggests that a high percentage of herds with digital dermatitis could be prevented. Management strategies to potentially prevent or reduce incidence of digital dermatitis on dairy operations include those related to biosecurity and 'cow hoof' environmental conditions.

Clinical, gross pathologic, and therapeutic studies were performed on a contagious, painful, wart-like digital disease of unknown etiology in California dairy cattle. The disease was called papillomatous digital dermatitis (PDD). Survey indicated that the disease spread geographically throughout southern California over the past few years. In 1991, 31% of herds had papillomatous digital dermatitis, whereas in 1994, 89% were affected. Increased incidence occurred during late spring and summer, 1-3 months after the rainy season. Within-herd morbidity ranged from 0.5% to 12% per month. Study of 93 cows in 10 drylot dairies revealed that 91% had characteristic circumscribed, erosive to papillomatous, intensely painful lesions often surrounded by a ridge of hyperkeratotic skin bearing hypertrophied hairs. Lesions were 2-6 cm across (88%), circular to oval (78%), and raised (59%) and had surfaces that were uniformly erosive and granular (31%), uniformly papillary (28%), or composites of both appearances (41%). Lesions were most frequently seen in lactating heifers (31%) and 3-year-old cows (43%). Clinical signs were characterized by lameness, with walking on toes and clubbing of hooves. Lesions exclusively involved the hind limbs in 82% of cows and the plantar/palmar regions in 84% of cows. Lesions had high (89%) prediliction for plantar/palmar skin bordering the interdigital space. Lesions exclusively involved either the medial or lateral digit in 10% and 28% of cows, respectively. In 50% of cows, both medial and lateral digits of individual limbs were involved; in most cows (31%), lesions apposed each other across the plantar interdigital space, whereas in others (19%), lesions confluently involved the entire plantar/palmar commissural skin folds. In another 12% of cows, lesions were axial. High proportions of lesions showed complete therapeutic responses to antibiotics: parenteral penicillin (9/9) and ceftiofur (41/44), and topical oxytetracycline (4/4). Recurrence or new lesion development occurred in 48% of cows reexamined 7-12 weeks after complete therapeutic response was observed. Overall, the findings indicated that PDD is a distinct disease entity of economic importance in which bacteria may play an important pathogenic role.

The bovine papillomavirus type 1 (BPV1) L2 protein purified from Escherichia coli was used as an antigen to produce monoclonal antibodies (MAbs). A total of 26 individual clones which recognized the BPV1 L2 protein were obtained. Using infectious BPV1 virus particles, 3 of the MAbs were found to interact with BPV1 virus particles. Binding of the MAbs to BPV1 was confirmed by immunoelectron microscopy. A set of 92 13-mer peptides overlapping by 8 amino acids spanning the entire BPV1 L2 protein was synthesized on a membrane and used to map the epitopes recognized by these antibodies. Seventeen linear epitopes were identified. Our results revealed that a sequence toward the N-terminus of the L2 protein (aa 61-123) is displayed on the virus surface, while the remaining L2 sequences are hidden inside the virus capsid. Although the polyclonal antisera raised against BPV1 L2 neutralized the BPV1 virus, we failed to detect any neutralizing activity for the 3 L2-specific monoclonal antibodies which bound to the BPV1 particles. This suggests that extra binding sites may be needed for neutralization. This study prompted us to propose a model about how L1 and L2 proteins may interact during infectious papillomavirus assembly.

During a long term experiment designed to identify the contribution of bovine papillomavirus type 4 (BPV-4), environmental mutagens and immunosuppressants to the development of carcinomas of the upper alimentary tract of cattle, there was evidence of latent papillomavirus infection. Papillomatosis-free animals, when immunosuppressed either by feeding bracken fern or by azathioprine treatment, developed skin warts containing either BPV-1 or BPV-2. Skin warts appeared also in an immunocompetent animal at sites of damaged skin. It was concluded that the animals harboured latent papillomavirus which was reactivated by immunosuppression and/or physical trauma, causing skin warts. Papillomavirus DNA was also detected in lymphocytes of both experimental and control animals, suggesting that one of the sites of latency may be the circulating lymphocyte.

Severe papillomatosis developed in the oral cavity and spread throughout the haired skin of the trunk and limbs of an 8-month-old female Chinese Shar Pei dog. The dog had received corticosteroids prior to referral, which was associated with the onset of demodecosis and papillomatosis. Papillomavirus structural antigens were detected in biopsies by immunohistochemistry using a panel of monoclonal and polyclonal antibodies. An 8.2-kilobase papillomavirus-specific DNA molecule was detected in the cutaneous lesions by high stringency Southern blot hybridization using a cloned canine oral papillomavirus DNA probe. Restriction enzyme analysis revealed that the virus in the cutaneous lesions was identical to the canine oral papillomavirus. Discontinuation of the steroids combined with the use of a mitocide, antibiotics, and an autogenous vaccine resolved the demodecosis and papillomatosis. This case report suggests that corticosteroid-induced immunosuppression can expand the tissue tropism of papillomaviruses.

Fifteen four-month old calves were inoculated, on five scarified sites on each side of the neck, with a suspension of ground wart tissue from a steer naturally infected with bovine papilloma virus 1. Warts started to appear about one month postinfection and were measurable in ten calves two months postinfection, when the trial started. After stratification on the size of the warts, all fifteen calves were allocated randomly to one of the following treatment groups: twice weekly intramuscular injections of 5 mg recombinant bovine interferon alpha I1 (rBoIFN alpha I1), weekly injection of 5 mg of rBoIFN alpha I1 or placebo, for three weeks. The biggest wart on each calf at the beginning of the trial was measured and photographs of all warts were taken weekly for five weeks. An analysis of covariance on the log of the volumes of warts during the five weeks of the trial showed a significant difference between groups (p = 0.026). Warts in treated groups tended to grow faster than in the placebo group.

Nucleotide sequences of bovine papillomavirus (BPV) DNA amplified by the polymerase chain reaction (PCR) from samples of equine sarcoid skin tumours were determined. All naturally occurring sarcoids (n = 58 tumours from 32 horses and 2 donkeys) contained BPV-DNA. All but 3 of the genome fragments belonged to the BPV type 1 strain (BPV-1); the remaining were BPV type 2. Similar results were obtained with cutaneous bovine papillomas used as controls (n = 20). One of the horses, carrying 2 sarcoids, was particularly interesting; one tumour contained BPV-1 DNA whilst the other sarcoid yielded BPV-2 DNA, suggesting that horses are not immune to super-infection. BPV-DNA was even amplified from the sarcoid samples which had yielded negative results in previous investigations when DNA isolated from the lesions was used in Southern blot hybridization with BPV probes. In addition, there was no detectable BPV-DNA in any equine or bovine tissue examined other than sarcoids or cutaneous bovine papillomas. Biopsies of normal skin surrounding lesions yielded exclusively negative results. The described nucleotide differences represent a natural genomic variation of this BPV type between geographically distant locations. The identical variations recovered from cattle and horses in Switzerland, a finding of great epidemiological interest, strongly suggest that a uniform variant of BPV-1 is one of the etiologic agents of equine sarcoid and bovine papilloma in a given region.

Gross abnormalities of the mammary glands of 1650 culled ewes were recorded. Clinically obvious lesions were detected in 211 (12.8 per cent) of udders; 77 per cent of lesions were abscesses. A generalised calcification of the whole of a gland was observed in 23 udders. It is concluded that abnormalities of the udder are an important reason for the culling ewes. The assessment of the cost-effectiveness of measures to reduce the incidence of mastitis would be worthwhile.

The two large open reading frames denoted L1 and L2 in the non-transforming region of the bovine papillomavirus type 1 (BPV-1) genome have been molecularly cloned to expression in Escherichia coli. Antisera against the E. coli-derived L1 and L2 protein reacted with BPV-1 in both enzyme-linked immunosorbent assays and immunoprecipitation reactions. Neutralization of BPV-induced transformation of mouse C127 cells was demonstrated most consistently with antisera against the L1 protein. E. coli-derived L1 protein protected calves against BPV-1 challenge after vaccination.