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The present study was conducted during the period from July, 2023 to January, 2024. Two clinical cases of cattle were reported with cutaneous papillomas, one near right umbilical region and another over the right hind teat of cattle. Both the animals were treated with a protocol designed such that it can regulate the secondary bacterial infection, speedy recovery of integument system and enhance the immune response for complete regression of the warts. The innate immune responses of infected animals were augmented with inactivated pathogen associated molecular patterns (PAMPs) as autogenous vaccine candidate. The warts were surgically excised, triturated in sterile PBS, inactivated with 0.5% formaline and prepared the autogenous vaccine. The sterility test of vaccine revealed that the vaccine was free from bacterial and fungal contaminants. The chemotherapy includes the use of drugs Thuja ointment, Inj. Enrofloxacin, Inj. Avil and Inj. Anthiomaline. The dose of the vaccine was 1 ml 20 kg-1 b.wt. subcutaneously and given at weekly intervals for a period of 4 weeks. It was observed that the treatment protocol was successfully effective and regression of warts was noticed from 2nd week onwards. By end of 4th week a complete recovery of the wart infected area was noticed with a black scar left behind. The formalin inactivated autogenous vaccine was effective, and applied for control of bovine papillomavirus infection in cattle with combination of chemotherapeutic drugs resulted in early regression of warts. [ABSTRACT FROM AUTHOR]

Bovine and ovine papillomaviruses (BPVs – OaPVs) are infectious agents that have an important role in bladder carcinogenesis of cattle. In an attempt to better understand territorial prevalence of papillomavirus genotypes and gain insights into their molecular pathway(s), a virological assessment of papillomavirus infection was performed on 52 bladder tumors in cattle using droplet digital polymerase chain reaction (ddPCR), an improved version of conventional PCR. ddPCR detected and quantified BPV DNA and mRNAs in all tumor samples, showing that these viruses play a determinant role in bovine bladder carcinogenesis. OaPV DNA and mRNA were detected and quantified in 45 bladder tumors. BPV14, BPV13, BPV2, OaPV2, OaPV1, and OaPV3 were the genotypes most closely related to bladder tumors. ddPCR quantified BPV1 and OaPV4 DNA and their transcripts less frequently. Western blot analysis revealed a significant overexpression of the phosphorylated platelet derived growth factor β receptor (PDGFβR) as well as the transcription factor E2F3, which modulate cell cycle progression in urothelial neoplasia. Furthermore, significant overexpression of calpain1, a Cys protease, was observed in bladder tumors related to BPVs alone and in BPV and OaPV coinfection. Calpain1 has been shown to play a role in producing free transcription factors of the E2F family, and molecular findings suggest that calpain family members work cooperatively to mutually regulate their protease activities in cattle bladder tumors. Altogether, these results showed territorial prevalence of BPV and OaPV genotypes and suggested that PDGFβR and the calpain system appeared to be molecular partners of both BPVs and OaPVs.

There is very little information available about transplacental infections by the papillomavirus in ruminants. However, recent evidence has emerged of the first report of vertical infections of bovine papillomavirus (BPV) in fetuses from naturally infected, pregnant cows. This study reports the coinfection of BPV and ovine papillomavirus (OaPV) in bovine fetuses from infected pregnant cows suffering from bladder tumors caused by simultaneous, persistent viral infections. Some molecular mechanisms involving the binary complex composed of Eras and platelet-derived growth factor β receptor (PDGFβR), by which BPVs and OaPVs contribute to reproductive disorders, have been investigated. A droplet digital polymerase chain reaction (ddPCR) was used to detect and quantify the nucleic acids of the BPVs of the Deltapapillomavirus genus (BPV1, BPV2, BPV13, and BPV14) and OaPVs belonging to the Deltapapillomavirus (OaPV1, OaPV2, and OaPV4) and Dyokappapapillomavirus (OaPV3) genera in the placenta and fetal organs (heart, lung, liver, and kidneys) of four bovine fetuses from four pregnant cows with neoplasia of the urinary bladder. A papillomaviral evaluation was also performed on the bladder tumors and peripheral blood of these pregnant cows. In all fetal and maternal samples, the genotype distribution of BPVs and OaPVs were evaluated using both their DNA and RNA. A BPV and OaPV coinfection was seen in bladder tumors, whereas only BPV infection was found in peripheral blood. The genotype distribution of both the BPVs and OaPVs detected in placentas and fetal organs indicated a stronger concordance with the viral genotypes detected in bladder tumors rather than in peripheral blood. This suggests that the viruses found in placentas and fetuses may have originated from infected bladders. Our study highlights the likelihood of vertical infections with BPVs and OaPVs and emphasizes the importance of gaining further insights into the mechanisms and consequences of this exposure. This study warrants further research as adverse pregnancy outcomes are a major source of economic losses in cattle breeding. [ABSTRACT FROM AUTHOR]

Sarcoids are common mesenchymal neoplasms of horses. Although there are few studies in which sarcoids have been followed over a long period of time, sarcoids are considered locally invasive and have been reported to frequently recur following surgical excision. Currently, no histological features have been identified to predict which sarcoids will recur after excision. The present study comprised 49 sarcoids for which histology sections were available and in which the recurrence status of the case was known. Each sarcoid was excised from a different horse. Overall, 12 of the 49 (24%) sarcoids recurred after surgical excision. Mitotic count (MC), cellularity, necrosis, nuclear pleomorphism, and inflammation of the sarcoids were evaluated histologically. Of these, MC correlated with recurrence. Four of 5 (80%) sarcoids with an MC ≥ 20 in 2.37 mm2 recurred, which was a significantly higher recurrence rate than that of sarcoids with an MC < 20, 8 of 44 cases recurred (18%), P =.0051. Clinical type was also found to correlate with recurrence. Three of 4 (75%) fibroblastic types recurred, which was a significantly higher recurrence rate than that of sarcoids with other clinical types, 9 of 45 cases (18%), P <.001. In addition, univariate Cox regression analysis confirmed fibroblastic type and MC ≥ 20 as significant predictors for recurrence (P =.016 and P =.005, respectively). To the authors' knowledge, this is the first large study examining recurrence rates in sarcoids, and the first time that histological features have been correlated with recurrence. [ABSTRACT FROM AUTHOR]

Abstract Bovine papillomavirus (BPV) infects cattle cells worldwide, leading to hyperproliferative lesions and the potential development of cancer, driven by E5, E6, and E7 oncoproteins along with other cofactors. E6 oncoprotein binds experimentally to various proteins, primarily paxillin and MAML1, as well as hMCM7 and CBP/p300. However, the molecular and structural mechanisms underlying BPV-induced malignant transformation remain unclear. Therefore, we have modeled the E6 oncoprotein structure from non-oncogenic BPV-5 and compared them with oncogenic BPV-1 to assess the relationship between structural features and oncogenic potential. Our analysis elucidated crucial structural aspects of E6, highlighting both conserved elements across genotypes and genotype-specific variations potentially implicated in the oncogenic process, particularly concerning primary target interactions. Additionally, we predicted the location of the hMCM7 binding site on the N-terminal of BPV-5 E6. This study enhances our understanding of the structural characteristics of BPV E6 oncoproteins and their interactions with host proteins, clarifying structural differences and similarities between high and low-risk BPVs. This is important to understand better the mechanisms involved in cell transformation in BPV infection, which could be used as a possible target for therapy.

Cutaneous bovine papillomatosis is caused by the bovine papillomavirus types (BPV-1 to -10). It is a contagious disease characterised by multiple skin lesions (tumours or growths) commonly in different body regions and is associated with huge economic losses. On 9th November, 2019 a client from the Gagi area of the Sokoto metropolis reported a case of pox-likegrown lesions on a one-year-old male crossed-bred Holstein-Friesian to the Aliyu Jodi Veterinary Clinic, Sokoto. There were ticks in the ear and beneath the tail on physical examination. The patient was diagnosed with cutaneous bovine papillomatosis. The condition was managed symptomatically, by excising the lesions and treatment using Ivermectin super® (Ivermectin 10 mg, Clorsulon 100 mg) subcutaneous (SC) injection, Pentstrep 20/25 inj.® (Procaine penicillin G 200 mg, Dihydrostreptomycin sulphate 250 mg) intramuscular (IM) injection, Flunixin (50 mg) intraveinous (IV) injection for 4 days and Multivitamin injection (x®). The cattle recovered with no history of recurrence or sign of skin damage. Symptomatic treatment is therefore recommended for cutaneous bovine papillomatosis and surgical excision should be carried out at mature (regressing stage) to avoid recurrence. [ABSTRACT FROM AUTHOR]

Teat papillomatosis is reported to be one of the factors causing mastitis and milk losses in dairy cattle. Little is known about bovine papillomavirus (BPV) circulation in the European cattle population, and no reports can yet be found about its prevalence in Polish herds. In this study, 177 BPV-like lesions were collected from teats of 109 slaughtered cows. BPV was identified in 39 of the examined animals, using PCR amplification and Sanger dideoxy sequencing. In total, 10 BPV types were isolated, among which the most common were infections caused by types 8 and 7. Macroscopically, "rice-grain" type lesions dominated (76%) and were mainly found on one teat (57.4%). The diversity of BPV types causing teat papillomatosis in Polish cows seems to be large, with nine already known types isolated and a new putative type found. The spread of new types among the worldwide cattle population can be seen for the first time, as type 25 and so called isolates BPV42 and BPV43 were found in the European cattle population. [ABSTRACT FROM AUTHOR]

Equine sarcoids (EqS) are fibroblast-derived skin tumors associated with bovine papillomavirus 1 and 2 (BPV-1 and -2). Based on Southern blotting, the BPV-1 genome was not found to be integrated in the host cell genome, suggesting that EqS pathogenesis does not result from insertional mutagenesis. Hence, CRISPR/Cas9 implies an interesting tool for selectively targeting BPV-1 episomes or genetically anchored suspected host factors. To address this in a proof-of-concept study, we confirmed the exclusive episomal persistence of BPV-1 in EqS using targeted locus amplification (TLA). To investigate the CRISPR/Cas9-mediated editing of BPV-1 episomes, primary equine fibroblast cultures were established and characterized. In the EqS fibroblast cultures, CRISPR-mediated targeting of the episomal E5 and E6 oncogenes as well as the BPV-1 long control region was successful and resulted in a pronounced reduction of the BPV-1 load. Moreover, the deletion of the equine Vimentin (VIM), which is highly expressed in EqS, considerably decreased the number of BPV-1 episomes. Our results suggest CRISPR/Cas9-based gene targeting may serve as a tool to help further unravel the biology of EqS pathogenesis. [ABSTRACT FROM AUTHOR]

There is very little information available about transplacental infections by the papillomavirus in ruminants. However, recent evidence has emerged of the first report of vertical infections of bovine papillomavirus (BPV) in fetuses from naturally infected, pregnant cows. This study reports the coinfection of BPV and ovine papillomavirus (OaPV) in bovine fetuses from infected pregnant cows suffering from bladder tumors caused by simultaneous, persistent viral infections. Some molecular mechanisms involving the binary complex composed of Eras and platelet-derived growth factor β receptor (PDGFβR), by which BPVs and OaPVs contribute to reproductive disorders, have been investigated. A droplet digital polymerase chain reaction (ddPCR) was used to detect and quantify the nucleic acids of the BPVs of the Deltapapillomavirus genus (BPV1, BPV2, BPV13, and BPV14) and OaPVs belonging to the Deltapapillomavirus (OaPV1, OaPV2, and OaPV4) and Dyokappapapillomavirus (OaPV3) genera in the placenta and fetal organs (heart, lung, liver, and kidneys) of four bovine fetuses from four pregnant cows with neoplasia of the urinary bladder. A papillomaviral evaluation was also performed on the bladder tumors and peripheral blood of these pregnant cows. In all fetal and maternal samples, the genotype distribution of BPVs and OaPVs were evaluated using both their DNA and RNA. A BPV and OaPV coinfection was seen in bladder tumors, whereas only BPV infection was found in peripheral blood. The genotype distribution of both the BPVs and OaPVs detected in placentas and fetal organs indicated a stronger concordance with the viral genotypes detected in bladder tumors rather than in peripheral blood. This suggests that the viruses found in placentas and fetuses may have originated from infected bladders. Our study highlights the likelihood of vertical infections with BPVs and OaPVs and emphasizes the importance of gaining further insights into the mechanisms and consequences of this exposure. This study warrants further research as adverse pregnancy outcomes are a major source of economic losses in cattle breeding.

A wart lesion was observed near the anus of a female Arabian horse housed in a private equine facility in Bucak District of Burdur Province. During the histopathological examination of the mass, equine sarcoid was revealed. Polymerase chain reaction (PCR) revealed the presence of bovine papillomavirus (BPV) type 10 and type 12 viral genomes in the tissue. It was observed that the combined treatment approach of PAPILEND™ ® cream + Zylexis™ + AlquermoldTM premix powder was beneficial in treating the sarcoid associated with BPV type 10 and type 12 on the anal region. No recurrence of the lesion was observed during the 6-month follow-up period. In conclusion, it is recommended to diagnose the presence of BPV in horses with warts and to investigate the efficacy of this combined treatment approach in larger populations. [ABSTRACT FROM AUTHOR]

Papillomaviruses, known as epitheliotropic, cause proliferation in the skin, mucosa, and different visceral organs. In this study, it was aimed to diagnose bovine papillomavirus (BPV) by using different methods in the lesion taken from twenty cattle with papillomas in different areas of the body and to reveal its molecular characterization. In our study, molecular, immunohistochemistry, and transmission electron microscopy (TEM) methods were used for virus identification. Additionally, sequencing analysis was used to ascertain the phylogenetic relationship between the obtained field strains and other isolates submitted to GenBank. Histopathological analyses of the collected samples were done in addition to diagnostic procedures. Intranuclear virus particles were detected when the papillomas were investigated with TEM. In PCR analyses using degenerate and type-specific primer sets, the presence of BPV nucleic acid was determined in 70% (14/20) and 90% (18/20) of the samples, respectively. No virus could be detected in PCR applications using MY 09/11 degenerate primer sets. Twenty animals of different ages, races, and genders included in the study by random sampling method from different herds were divided into 4 groups according to the body regions where the lesions were located. Sequence analysis was performed on a sample from each group that showed strong positivity in the PCR technique using FAP 59/64 degenerate primer set and type-specific primer set. Sequence analyses were performed using FAP 59/64 degenerate primers of amplicons for phylogenetic research. In these analyses, three of the isolated strains were identified as BPV-1, which is in the Deltapapillomavirus 4 genus, and one as BPV-2. As a result of the study, it was concluded that molecular and phylogenetic studies using type-specific primers are more beneficial in order to fully reveal the etiology of papillomatosis in cattle and it would be correct to determine BPV types before prophylactic (vaccine, etc.) applications. [ABSTRACT FROM AUTHOR]

Horses and other equid species are frequently affected by bovine papillomavirus type 1 and/or 2 (BPV1, BPV2)-induced skin tumors termed sarcoids. Although sarcoids do not metastasize, they constitute a serious health problem due to their BPV1/2-mediated resistance to treatment and propensity to recrudesce in a more severe, multiple form following accidental or iatrogenic trauma. This review provides an overview on BPV1/2 infection and associated immune escape in the equid host and presents early and recent immunotherapeutic approaches in sarcoid management. [ABSTRACT FROM AUTHOR]

Background: Ocular squamous cell carcinomas (OSCCs) in cattle has been studied for many years, but no definite etiology has been established. Squamous cell carcinomas (SCCs) may occur in different body parts of cattle. Depending on the location, it can cause an economic loss of varying degrees. Aims: The aim of this study was to investigate the causes of OSCCs in the eye region of cattle. Methods: Sixty tumoral masses taken form 60 cattle with proliferation in the eye region that were collected between the years 2012-2022 were used. These cases were admitted to our department for routine diagnosis. The tissues were diagnosed as OSCC using histopathological methods. The presence of bovine papillomavirus (BPV), one of the causative factors, was investigated using immunohistochemical and polymerase chain reaction (PCR). Results: Macroscopically masses were nodular or cauliflower-like and fragile and had hemorrhagic surfaces. Considering the keratin pearls, tumoral islands, and squamous differentiation, 20 out of 60 cases were classified as well, 20 as moderately, and 20 as poorly-differentiated OSCCs. 47 of the 60 cases were BPV positive using immunohistochemical methods. However, BPV nucleic acid was detected in only two cases with PCR. Only one of the cases could be sequenced. After phylogenetic analysis, virus strain was identified as BPV-1. Conclusion: Our results indicated that papillomaviruses can contribute to the development of OSCCs, in both precursor lesions and also advanced stage OSCCs. We found that BPV-1 has a possible causative role; however, more studies are needed to investigate the role of other viral agents and their interaction with secondary factors. [ABSTRACT FROM AUTHOR]

Equine sarcoids are common, locally aggressive skin tumors induced by bovine papillomavirus types 1, 2, and possibly 13 (BPV1, BPV2, BPV13). Current in vitro models do not mimic de novo infection. We established primary fibroblasts from horse skin and succeeded in infecting these cells with native BPV1 and BPV2 virions. Subsequent cell characterization was carried out by cell culture, immunological, and molecular biological techniques. Infection of fibroblasts with serial 10-fold virion dilutions (2 × 106-20 virions) uniformly led to DNA loads settling at around 150 copies/cell after four passages. Infected cells displayed typical features of equine sarcoid cells, including hyperproliferation, and loss of contact inhibition. Neither multiple passaging nor storage negatively affected cell hyperproliferation, viral DNA replication, and gene transcription, suggestive for infection-mediated cell immortalization. Intriguingly, extracellular vesicles released by BPV1-infected fibroblasts contained viral DNA that was most abundant in the fractions enriched for apoptotic bodies and exosomes. This viral DNA is likely taken up by non-infected fibroblasts. We conclude that equine primary fibroblasts stably infected with BPV1 and BPV2 virions constitute a valuable near-natural model for the study of yet unexplored mechanisms underlying the pathobiology of BPV1/2-induced sarcoids. [ABSTRACT FROM AUTHOR]

Equine sarcoids are common non-metastasising skin tumours in horses, associated with bovine papillomavirus (BPV) infection. Six subtypes are recognised (occult, verrucose, nodular, fibroblastic, mixed and malevolent lesions), with variable clinical behaviour. The pathophysiology underlying varying tumour phenotype is poorly understood, and previous data on associations with viral load have been conflicting. To better understand this clinical variation, we investigated associations between tumour subtype and viral load, viral early protein gene expression, and expression of 10 host genes by quantitative polymerase chain reaction in 27 sarcoids and 5 normal skin samples. Viral DNA copy number did not differ between subtypes but was significantly higher in animals with fewer tumours. Expression of BPV E2 and E6 was higher in occult lesions compared to fibroblastic or nodular lesions, while E5 expression was higher in previously-treated lesions. Of the host genes, only IL6 and IL1B differed between subtypes, with higher expression in fibroblastic lesions, while IL10 and CCL5 were elevated compared to skin in all lesion types, and elevations in TNF and TGFB1 were significant for occult lesions only. Expression of TLR9 , ATR , VEGFA and PTGS2 in sarcoids was not significantly different from normal skin, suggesting differences between BPV and human papillomavirus tumorigenesis. Results for BPV viral load and gene expression differed from previous reports and are insufficient to explain the spectrum of tumour phenotypes. Activation of both pro-inflammatory and anti-inflammatory immune pathways in sarcoids could influence tumour growth and effective immune responses, and the contribution of specific infiltrating immune cells requires further investigation. • Bovine papillomavirus (BPV) DNA was present in all equine sarcoid tumour types but not normal skin. • BPV early protein gene expression, but not DNA copy number, was higher in occult lesions. • BPV transforming protein gene E5 was more highly expressed in previously treated lesons. • Both pro- and anti-inflammatory cytokines were upregulated in all tumour subtypes. • IL6 and IL1β mRNA expression was increased more in fibroblastic sarcoids than in other subtypes. [ABSTRACT FROM AUTHOR]

Teat papillomatosis is reported to be one of the factors causing mastitis and milk losses in dairy cattle. Little is known about bovine papillomavirus (BPV) circulation in the European cattle population, and no reports can yet be found about its prevalence in Polish herds. In this study, 177 BPV-like lesions were collected from teats of 109 slaughtered cows. BPV was identified in 39 of the examined animals, using PCR amplification and Sanger dideoxy sequencing. In total, 10 BPV types were isolated, among which the most common were infections caused by types 8 and 7. Macroscopically, “rice-grain” type lesions dominated (76%) and were mainly found on one teat (57.4%). The diversity of BPV types causing teat papillomatosis in Polish cows seems to be large, with nine already known types isolated and a new putative type found. The spread of new types among the worldwide cattle population can be seen for the first time, as type 25 and so called isolates BPV42 and BPV43 were found in the European cattle population.

Equine sarcoids (EqS) are fibroblast-derived skin tumors associated with bovine papillomavirus 1 and 2 (BPV-1 and -2). Based on Southern blotting, the BPV-1 genome was not found to be integrated in the host cell genome, suggesting that EqS pathogenesis does not result from insertional mutagenesis. Hence, CRISPR/Cas9 implies an interesting tool for selectively targeting BPV-1 episomes or genetically anchored suspected host factors. To address this in a proof-of-concept study, we confirmed the exclusive episomal persistence of BPV-1 in EqS using targeted locus amplification (TLA). To investigate the CRISPR/Cas9-mediated editing of BPV-1 episomes, primary equine fibroblast cultures were established and characterized. In the EqS fibroblast cultures, CRISPR-mediated targeting of the episomal E5 and E6 oncogenes as well as the BPV-1 long control region was successful and resulted in a pronounced reduction of the BPV-1 load. Moreover, the deletion of the equine Vimentin (VIM), which is highly expressed in EqS, considerably decreased the number of BPV-1 episomes. Our results suggest CRISPR/Cas9-based gene targeting may serve as a tool to help further unravel the biology of EqS pathogenesis.

Abstract Background Bovine papillomavirus (BPV) types 1 and 2 play a central role in the etiology of the most common neoplasm in horses, the equine sarcoid. The unknown mechanism behind the unique variety in clinical presentation on the one hand and the host dependent clinical outcome of BPV-1 infection on the other hand indicate the involvement of additional factors. Earlier studies have reported the potential functional significance of intratypic sequence variants, along with the existence of sarcoid-sourced BPV variants. Therefore, intratypic sequence variation seems to be an important emerging viral factor. This study aimed to give a broad insight in sarcoid-sourced BPV variation and explore its potential association with disease presentation. Methods In order to do this, a nanopore sequencing approach was successfully optimized for screening a wide spectrum of clinical samples. Specimens of each tumour were initially screened for BPV-1/-2 by quantitative real-time PCR. A custom-designed primer set was used on BPV-positive samples to amplify the complete viral genome in two multiplex PCR reactions, resulting in a set of overlapping amplicons. For phylogenetic analysis, separate alignments were made of all available complete genome sequences for BPV-1/-2. The resulting alignments were used to infer Bayesian phylogenetic trees. Results We found substantial genetic variation among sarcoid-derived BPV-1, although this variation could not be linked to disease severity. Several of the BPV-1 genomes had multiple major deletions. Remarkably, the majority of them cluster within the region coding for late viral genes. Together with the extensiveness (up to 603 nucleotides) of the described deletions, this suggests an altered function of L1/L2 in disease pathogenesis. Conclusions By generating a significant amount of complete-length BPV genomes, we succeeded to introduce next-generation sequencing into veterinary research focusing on the equine sarcoid, thus facilitating the first report of both nanopore-based sequencing of complete sarcoid-sourced BPV-1/-2 and the simultaneous nanopore sequencing of multiple complete genomes originating from a single clinical sample.

Simple Summary: Expression of cell-cycle regulatory proteins pRB, Cyclin D1, and p53 is not associated with recurrence rates of equine sarcoids. Sarcoids are common tumors of equids, and since the pathogenesis and Bovine Papillomavirus (BPV) mechanism of tumorigenesis is not fully understood yet, we investigated the expression of cell cycle regulatory proteins pRB, Cyclin D1, and p53 to understand whether BPV and Human Papillomavirus (HPV) share similar mechanisms of action. The expression pattern of these proteins in a series of BPV-positive equine sarcoids is different from HPV-induced tumors. Moreover, their expression is not correlated with the recurrence or occurrence of sarcoids in new body sites. Sarcoids are among the most common tumors diagnosed in equids; their association with bovine papillomaviruses (BPV) infection has been widely reported, but the mechanism of carcinogenesis has not been fully elucidated. To verify whether BPV infection causes dysregulation of the pRb-Cyclin D1-p16CDKN2A-p53 pathway as reported for human papillomavirus (HPV), the study employed immunohistochemistry to test 55 equine sarcoid biopsies for the expression of pRb, Cyclin D1, and p53 cell cycle regulatory proteins and to evaluate the proliferative rate through Ki67. High Cyclin D1 and pRb expression were observed in 51% and 80% of cases, respectively, while low expression was observed in 49% and 20% of cases, respectively. Significantly higher Ki67 proliferation indexes were observed in fibroblastic, nodular, and mixed sarcoids compared to the occult and verrucous. High proliferation was significantly associated with high Cyclin D1 expression. In contrast with previous studies, p53 positivity was not observed in the cases examined in this study. Moreover, follow-up analysis revealed that fibroblastic, mixed sarcoids were associated with significantly higher local recurrence rates while the verrucous subtype was associated with higher rates of new sarcoid development at distant sites. [ABSTRACT FROM AUTHOR]

Bovine papillomavirus type 1 (BPV1) is an oncogenic virus that causes lesions and cancer in infected cattle. Despite being one of the most studied genotypes in the family and occurring in herds worldwide, there are currently no vaccines or drugs for its control. The viral E6 oncoprotein plays a crucial role in infection by this virus, making it a promising target for the development of new therapies. In this regard, we integrated structure-based virtual screening approaches, drug repositioning, and molecular dynamics to identify approved drugs with the potential to inhibit BPV1 E6. Our results reveal that Lumacaftor and MK-3207 are promising candidates for controlling BPV1 infection. The findings of this study may contribute to the development of E6 oncoprotein blockers in an accelerated and cost-effective manner., (© 2024 The Societies and John Wiley & Sons Australia, Ltd.)

Background: Bovine papillomavirus types 1 and 2 (BPV1 and BPV2) are accepted aetiological agents of equine sarcoids. Recently, genetically similar BPV13 has been identified from equine sarcoids in Brazil. Objectives: To determine whether BPV13 DNA can be also found in sarcoid‐affected horses in Austria, and donkeys in Northern Italy and the UK, and should hence be considered in the context of vaccine‐mediated sarcoid prevention. Study design: Cross sectional study. Methods: A total of 194 archival, equine and asinine DNA isolates derived from confirmedly delta‐BPV‐positive tumours were subjected to quality control by photometric analysis and equine beta‐actin PCR. Isolates with DNA concentrations >0.9 ng/µl and confirmed PCR‐compatibility (n = 135) were subsequently screened for the presence of BPV13 DNA using BPV13‐specific PCR primers for amplification of a 771 bp region comprising the BPV13 E5 gene. Results: BPV13 E5 PCR scored negative for all 135 samples. Included positive, negative and no‐template controls yielded anticipated results, thus confirming reliability of obtained data. Main limitations: Moderate number of tested tumour DNA extracts (n = 135; equivalent to 127 tumour‐affected equids). Conclusions: Despite its moderate size, the sample was considered representative enough to suggest a low occurrence of BPV13 in Austria, as it randomly comprised equine patients of different breed, age, gender, and European provenience. BPV13 was not associated with tested sarcoids in rescued donkeys originating from several other European countries. Large‐scale BPV13 screenings are necessary to allow for a more precise estimation of the prevalence and distribution of BPV13 infections in European equids suffering from sarcoid disease. [ABSTRACT FROM AUTHOR]

Horses and other equid species are frequently affected by bovine papillomavirus type 1 and/or 2 (BPV1, BPV2)-induced skin tumors termed sarcoids. Although sarcoids do not metastasize, they constitute a serious health problem due to their BPV1/2-mediated resistance to treatment and propensity to recrudesce in a more severe, multiple form following accidental or iatrogenic trauma. This review provides an overview on BPV1/2 infection and associated immune escape in the equid host and presents early and recent immunotherapeutic approaches in sarcoid management.

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Bovine and ovine papillomaviruses (BPVs - OaPVs) are infectious agents that have an important role in bladder carcinogenesis of cattle. In an attempt to better understand territorial prevalence of papillomavirus genotypes and gain insights into their molecular pathway(s), a virological assessment of papillomavirus infection was performed on 52 bladder tumors in cattle using droplet digital polymerase chain reaction (ddPCR), an improved version of conventional PCR. ddPCR detected and quantified BPV DNA and mRNAs in all tumor samples, showing that these viruses play a determinant role in bovine bladder carcinogenesis. OaPV DNA and mRNA were detected and quantified in 45 bladder tumors. BPV14, BPV13, BPV2, OaPV2, OaPV1, and OaPV3 were the genotypes most closely related to bladder tumors. ddPCR quantified BPV1 and OaPV4 DNA and their transcripts less frequently. Western blot analysis revealed a significant overexpression of the phosphorylated platelet derived growth factor β receptor (PDGFβR) as well as the transcription factor E 2 F 3 , which modulate cell cycle progression in urothelial neoplasia. Furthermore, significant overexpression of calpain1, a Cys protease, was observed in bladder tumors related to BPVs alone and in BPV and OaPV coinfection. Calpain1 has been shown to play a role in producing free transcription factors of the E 2 F family, and molecular findings suggest that calpain family members work cooperatively to mutually regulate their protease activities in cattle bladder tumors. Altogether, these results showed territorial prevalence of BPV and OaPV genotypes and suggested that PDGFβR and the calpain system appeared to be molecular partners of both BPVs and OaPVs.

Background: Bovine papillomavirus (BPV) types 1 and 2 play a central role in the etiology of the most common neoplasm in horses, the equine sarcoid. The unknown mechanism behind the unique variety in clinical presentation on the one hand and the host dependent clinical outcome of BPV-1 infection on the other hand indicate the involvement of additional factors. Earlier studies have reported the potential functional significance of intratypic sequence variants, along with the existence of sarcoid-sourced BPV variants. Therefore, intratypic sequence variation seems to be an important emerging viral factor. This study aimed to give a broad insight in sarcoid-sourced BPV variation and explore its potential association with disease presentation. Methods: In order to do this, a nanopore sequencing approach was successfully optimized for screening a wide spectrum of clinical samples. Specimens of each tumour were initially screened for BPV-1/-2 by quantitative real-time PCR. A custom-designed primer set was used on BPV-positive samples to amplify the complete viral genome in two multiplex PCR reactions, resulting in a set of overlapping amplicons. For phylogenetic analysis, separate alignments were made of all available complete genome sequences for BPV-1/-2. The resulting alignments were used to infer Bayesian phylogenetic trees. Results: We found substantial genetic variation among sarcoid-derived BPV-1, although this variation could not be linked to disease severity. Several of the BPV-1 genomes had multiple major deletions. Remarkably, the majority of them cluster within the region coding for late viral genes. Together with the extensiveness (up to 603 nucleotides) of the described deletions, this suggests an altered function of L1/L2 in disease pathogenesis. Conclusions: By generating a significant amount of complete-length BPV genomes, we succeeded to introduce next-generation sequencing into veterinary research focusing on the equine sarcoid, thus facilitating the first report of both nanopore-based sequencing of complete sarcoid-sourced BPV-1/-2 and the simultaneous nanopore sequencing of multiple complete genomes originating from a single clinical sample. [ABSTRACT FROM AUTHOR]

Sarcoids are the most common cutaneous tumor of equids and are caused by bovine papillomavirus (BPV). Different clinical subtypes of sarcoids are well characterized clinically but not histologically, and it is not known whether viral activity influences the clinical or histological appearance of the tumors. The aim of this study was to verify whether the development of different clinical types of sarcoids or the presence of certain histological features were associated with BPV distribution within the tumor. The presence of BPV was assessed by polymerase chain reaction (PCR) and visualized in histological sections by chromogenic in situ hybridization (CISH) in 74 equine sarcoids. Furthermore, to better characterize the molecular features of neoplastic cells, immunohistochemistry for S100, smooth muscle actin-α (αSMA), and fibroblast-associated protein-α (FAPα) was performed. The presence of BPV was confirmed in all tissues examined by either or both PCR and CISH (72/74, 97% each). Of 70/74 CISH-positive cases, signal distribution appeared as either diffuse (61/70, 87%) or subepithelial (9/70, 13%); the latter was more frequently observed in the verrucous subtype. However, no statistically significant association was found between clinical subtypes and specific histological features or hybridization pattern. Moreover, CISH signal for BPV was not detected in the epidermis overlying sarcoids nor in the tissue surrounding the neoplasms. By immunohistochemistry, αSMA confirmed the myofibroblastic differentiation of neoplastic cells in 28/74 (38%) sarcoids. Using tissue microarrays, FAPα labelling was observed in neoplastic fibroblasts of all sarcoids, suggesting this marker as a potential candidate for the immunohistochemical diagnosis of sarcoids. [ABSTRACT FROM AUTHOR]

Bovine papillomavirus (BPV) types 1 and 2 are recognized as the main cause of equine sarcoids. However, some studies report that up to a quarter of these tumors do not contain detectible BPV1 or BPV2 DNA. The absence of detectible BPV1 or BPV2 in these sarcoids suggests the possible involvement of other papillomavirus types. Currently, five deltapapillomaviruses are recognized to cause mesenchymal neoplasia after cross-species infection. In addition to BPV1 and BPV2, BPV13 has been associated with equine sarcoids in Brazil, BPV14 has been associated with feline sarcoids, and Ovis aries papillomavirus 2 caused a sarcoid-like lesion in a pig. To investigate the cause of equine sarcoids, PCR primers were developed to specifically amplify each of the five different deltapapillomaviruses that have been associated with mesenchymal neoplasia. The specificity of these primers was confirmed using samples of formalin-fixed tissue known to contain each PV type. These primers allow rapid and sensitive detection of deltapapillomavirus DNA in equine sarcoids. As studies have revealed marked regional variability in the cause of equine sarcoids, these primers will be useful to determine the predominant PV type causing sarcoids in a region. Additionally, there is a single report describing mixed infections by BPV1 and BPV2 in equine sarcoids. The specific primer sets are expected to enable more sensitive detection of mixed infections in equine sarcoids. Determining the cause of equine sarcoids is important as vaccines are developed to prevent these common malignant neoplasms. [ABSTRACT FROM AUTHOR]

Objective. To identify by molecular techniques the presence of bovine papillomavirus (BPV) in an equine sarcoid, and to carry out its histological characterization. Materials and methods. Using a sarcoid lesion from a Pinto Americano mare, nucleic acid extraction and identification by molecular techniques was performed. A partial region of the gene corresponding to the L1 segment of papillomavirus was amplified by polymerase chain reaction, then it was sequenced and analyzed using BLAST algorithm. Hematoxylin-eosin staining of the tissue was performed and analyzed under a 100X light microscope. Results. BPV-2 was detected in the equine sarcoid lesion, and the lesion was classified as nodular according to its morphological and histological characteristics. Histopathology showed a fibrotic lesion, with exophytic neoplasia and expansion of the spinous layer. Conclusions. The study established for first time the presence of BPV-2 in an equine sarcoid in Costa Rica using molecular techniques and its association with a nodular-type sarcoid. [ABSTRACT FROM AUTHOR]

Bovine papillomavirus (BPV) are a cause for global concern due to their wide distribution and the wide range of benign and malignant diseases they are able to induce. Those lesions include cutaneous and upper digestive papillomas, multiple histological types of urinary bladder cancers—most often associated with BPV1 and BPV2—and squamous cell carcinomas of the upper digestive system, associated with BPV4. Clinical, epidemiological and experimental evidence shows that exposure to bracken fern (Pteridium spp.) and other related ferns plays an important role in allowing viral persistence and promoting the malignant transformation of early viral lesions. This carcinogenic potential has been attributed to bracken illudane glycoside compounds with immune suppressive and mutagenic properties, such as ptaquiloside. This review addresses the role of BPV in tumorigenesis and its interactions with bracken illudane glycosides. Current data indicates that inactivation of cytotoxic T lymphocytes and natural killer cells by bracken fern illudanes plays a significant role in allowing viral persistence and lesion progression, while BPV drives unchecked cell proliferation and allows the accumulation of genetic damage caused by chemical mutagens. Despite limited progress in controlling bracken infestation in pasturelands, bracken toxins remain a threat to animal health. The number of recognized BPV types has steadily increased over the years and now reaches 24 genotypes with different pathogenic properties. It remains essential to widen the available knowledge concerning BPV and its synergistic interactions with bracken chemical carcinogens, in order to achieve satisfactory control of the livestock losses they induce worldwide.

Equine sarcoids are common, locally aggressive skin tumors induced by bovine papillomavirus types 1, 2, and possibly 13 (BPV1, BPV2, BPV13). Current in vitro models do not mimic de novo infection. We established primary fibroblasts from horse skin and succeeded in infecting these cells with native BPV1 and BPV2 virions. Subsequent cell characterization was carried out by cell culture, immunological, and molecular biological techniques. Infection of fibroblasts with serial 10-fold virion dilutions (2 × 106-20 virions) uniformly led to DNA loads settling at around 150 copies/cell after four passages. Infected cells displayed typical features of equine sarcoid cells, including hyperproliferation, and loss of contact inhibition. Neither multiple passaging nor storage negatively affected cell hyperproliferation, viral DNA replication, and gene transcription, suggestive for infection-mediated cell immortalization. Intriguingly, extracellular vesicles released by BPV1-infected fibroblasts contained viral DNA that was most abundant in the fractions enriched for apoptotic bodies and exosomes. This viral DNA is likely taken up by non-infected fibroblasts. We conclude that equine primary fibroblasts stably infected with BPV1 and BPV2 virions constitute a valuable near-natural model for the study of yet unexplored mechanisms underlying the pathobiology of BPV1/2-induced sarcoids.

Sarcoids are among the most common tumors diagnosed in equids; their association with bovine papillomaviruses (BPV) infection has been widely reported, but the mechanism of carcinogenesis has not been fully elucidated. To verify whether BPV infection causes dysregulation of the pRb-Cyclin D1-p16CDKN2A-p53 pathway as reported for human papillomavirus (HPV), the study employed immunohistochemistry to test 55 equine sarcoid biopsies for the expression of pRb, Cyclin D1, and p53 cell cycle regulatory proteins and to evaluate the proliferative rate through Ki67. High Cyclin D1 and pRb expression were observed in 51% and 80% of cases, respectively, while low expression was observed in 49% and 20% of cases, respectively. Significantly higher Ki67 proliferation indexes were observed in fibroblastic, nodular, and mixed sarcoids compared to the occult and verrucous. High proliferation was significantly associated with high Cyclin D1 expression. In contrast with previous studies, p53 positivity was not observed in the cases examined in this study. Moreover, follow-up analysis revealed that fibroblastic, mixed sarcoids were associated with significantly higher local recurrence rates while the verrucous subtype was associated with higher rates of new sarcoid development at distant sites.

Background: Bovine papillomatosis is a type of proliferative tumor disease of skin and mucosae caused by bovine papillomavirus (BPV). As a transboundary and emerging disease in cattle, it poses a potential threat to the dairy industry. Objectives: The aim of this study is to detect and clarify the genetic diversity of BPV circulating in dairy cows in Xinjiang, China. Methods: 122 papilloma skin lesions from 8 intensive dairy farms located in different regions of Xinjiang, China were detected by polymerase chain reaction. The genetic evolution relationships of various types of BPVs were analyzed by examining this phylogenetic tree. Results: Ten genotypes of BPV (BPV1, BPV2, BPV3, BPV6, BPV7, BPV8, BPV10, BPV11, BPV13, and BPV14) were detected and identified in dairy cows. These were the first reported detections of BPV13 and BPV14 in Xinjiang, Mixed infections were detected, and there were geographical differences in the distribution of the BPV genotypes. Notably, the BPV infection rate among young cattle (< 1-year-old) developed from the same supply of frozen sperm was higher than that of the other young cows naturally raised under the same environmental conditions. Conclusions: Genotyping based on the L1 gene of BPV showed that BPVs circulating in Xinjiang China displayed substantial genetic diversity. This study provided valuable data at the molecular epidemiology level, which is conducive to developing deep insights into the genetic diversity and pathogenic characteristics of BPVs in dairy cows. [ABSTRACT FROM AUTHOR]

A 23-year-old Falabella gelding kept in Tochigi, Japan, for more than 20 years presented with a recurrent mass of the glans penis that was first noticed about a year earlier. Partial phallectomy was performed with no adjunctive therapy for local regrowth of the mass. The horse was euthanized 3 months after surgery for urinary retention due to suspected regrowth. The resected mass affected the genital and urethral mucosa of the glans penis, and was diagnosed as equine sarcoid by histopathology and identification of bovine papillomavirus (BPV) DNA. Phylogenetic analysis of the BPV genome of the sarcoid showed high sequence homology to BPV type 1 (BPV-1) from Hokkaido, Japan, suggesting a geographical relationship for BPV-1 in Japan. [ABSTRACT FROM AUTHOR]

Abstract Background Bovine papillomavirus (BPV) belongs to the Papillomaviridae family and infects epithelial cells of bovines and closely related animals, causing hyperproliferative lesions known as warts or papillomas, which may regress or progress to form benign or malignant tumors. The virus enters the host cell and interacts with it by altering the regulation of genes that are responsible for controlling the cell cycle, thus triggering lesion formation. It is not yet known which host genes are regulated by viral infection. Therefore, the objective of this study was to make use of next-generation RNA sequencing methods to identify differentially expressed genes associated with BPV infection, which might elucidate possible marker genes that could be used to control the disease. Results Transcriptome analysis revealed that 1343 genes were differentially regulated (FDR

In this study, the digital droplet polymerase chain reaction (ddPCR) was used to quantify circulating bovine papillomavirus (BPV; genus: Deltapapillomavirus) DNA levels in blood samples from 25 clinically normal cows and 15 cows with chronic enzootic haematuria due to papillomavirus‐associated bladder tumours. ddPCR detected BPV DNA in 95% of all the samples (i.e. in 24 of the clinically normal cows and 14 of the diseased animals), whereas quantitative real‐time PCR (qPCR) detected it in only 57.5% of the same blood samples, with percentage differences between ddPCR and qPCR being statistically significant (p‐value ≤.05), according to chi‐squared test. Furthermore, ddPCR detected BPV infections by a single genotype and by multiple genotypes in 37% and 63% of the cows, whereas qPCR detected these in 16% and 16%. Of the two assays, ddPCR was the more sensitive and accurate clinical diagnostic tool, allowing the detection of otherwise undetectable BPV genotypes, and consequently, a higher number of BPV co‐infections. qPCR failed to detect many BPV co‐infections by multiple genotypes. Therefore, ddPCR may be an essential tool for improving diagnostic procedures, allowing the identification of the genotypic distribution of BPV and a better understanding about the territorial divergence, if any, of the BPV prevalence in different areas. No significant differences in the blood viral load estimations were observed between the two animal groups, suggesting that the bloodstream could be a site of primary infection. Finally, as BPV DNA was detected in cows affected by non‐invasive urothelial tumours, including papilloma and papillary urothelial neoplasms of low malignant potential, the circulating BPVs appeared to be independent of the status of urothelial neoplasms. Therefore, unlike in humans, circulating BPVs cannot be an actual prognostic marker of urothelial tumours in cows. [ABSTRACT FROM AUTHOR]

Equine sarcoid is the most common skin tumor of horses. Clinically, it occurs as a locally invasive, fibroblastic, wart-like lesion of equine skin, which has 6 clinical classes: occult, verrucose, nodular, fibroblastic, mixed, and malignant. Sarcoids may be single but multiple lesions are more frequent. The typical histological feature is increased density of dermal fibroblasts which form interlacing bundles and whorls within the dermis. Lesions are mostly persistent, resist therapy, and tend to recur following treatment. In general, sarcoids are not fatal but their location, size, and progression to the more aggressive form may lead to the withdrawal of a horse from use and serious infringement of their welfare leading to the loss of valuable animals. Bovine papillomavirus (BPV) type 1 and less commonly type 2 contribute to the development of equine sarcoid. The viral genome and proteins are detected in a high percentage of cases. Furthermore, viral oncoprotein activity leads to changes in the fibroblastic tissue similar to changes seen in other types of tumors. Equine sarcoids are characterized by a loss of tumor suppressor activity and changes allowing abnormal formation of the affected tissue, as well as y immune defense abnormalities that weaken the host's immune response. This impaired immune response to BPV infection appears to be crucial for the development of lesions that do not spontaneously regress, as occurs in BPV-infected cows. [ABSTRACT FROM AUTHOR]

We have previously reported that bovine papillomavirus type 1 (BPV1) can replicate its genome and produces infectious virus-like particles in short-term BPV1 virion-infected Sacharomyces cerevisiae (Zhao and Frazer, 2002). Here, we report viral RNA transcription and L1 capsid protein expression in long-term BPV1 virion-infected S. cerevisiae culture. Northern blot hybridization showed that viral RNA was detected in long-term BPV1-infected S. cerevisiae cultures (82-108 days). The levels of the viral RNA transcription varied significantly over the long time period, which showed active transcription at an early stage (Day 3 to Day 16), weak transcription at a middle stage (Day 23 to Day 45) and stable transcription at the late stage of culture (Day 55 to Day 82/85/95). Three major BPV1 transcripts of 4.3, 2.6 and 1.8 Kb were identified, with 4.3 Kb a minor transcript and the 1.8 Kb the most prominent transcript compared with the 2.6 Kb species. Immunoblotting showed that L1 capsid protein was expressed, with its variable amounts corresponding to the levels of RNA transcription over the time period. 35S-methionine/cysteine labeling and immunoprecipitation proved that the detected L1 protein was newly synthesized in BPV1-infected S. cerevisiae cultures. 33.3-54.2% of the cell colonies expressed L1 protein. Thus, the S. cerevisiae system, as a promising model, may be used not only for the study of virus like particle formation of BPV1 in vitro, but also for further functional analysis of individual viral genes in BPV1 life cycle. [ABSTRACT FROM AUTHOR]

Bovine papillomavirus (BPV) occurs worldwide and has myriad signs, including cutaneous papillomas, fibromas and fibropapillomas. Histology and PCR were used to identify the presence of BPV in tissue samples collected from cattle manifesting skin lesions suggestive of papillomas, fibromas and fibropapillomas in production units in the state of San Luis Potosí, Mexico. Eleven skin biopsies were taken from animals between 5 and 18 months' age in stabled, semi-stabled and pastured beef and dairy production systems. Lesions were suggestive of papillomas, fibropapillomas and squamous cell carcinomas. Samples were evaluated by histopathology. Detection of BPV was also done using DNA extracted from the samples and analyzed by PCR with the FAP59/FAP64 and MY09/MY11 oligonucleotide pairs. The lesions were classified into fibromas (45.45 %) and fibropapillomas (54.54 %). Lesion type distribution exhibited no patterns by anatomical location, animal age, production system or end purpose. Most (72.72 %, n= 8) of the samples were positive for BPV by PCR; 45.45 % (n= 5) with the FAP pair and 54.54 % (n= 6) with the MY pair. This is the first study identifying the presence of BPV in San Luis Potosí. The results will be useful in establishing detection and control measures to improve production system health measures and end product quality. [ABSTRACT FROM AUTHOR]

Cutaneous warts are the common clinical feature of infection with Bovine papillomavirus (BPV), and it is commonly known as bovine papillomatosis. It causes significant economic losses, especially in the dairy sector. The aim of this study was surveillance of the circulating strains of BPV in four Egyptian governorates and characterization by electron microscopy. Warts skin lesions and whole blood from seventy-eight native breed cattle were obtained. Molecular detection using two different sets of primers, phylogenetic analysis, and electron microscopy were carried out. The obtained results showed that using FAP59/FAP64 primer set is more sensitive than the MY09/My11 primer set in the detection of the papilloma L1 gene either in the blood or in the skin lesion. Sequence analysis of the partially amplified L1 gene revealed 4 different strains belonging to Deltapapillomavirus 4. Only Alfayoum_Deltapapillomavirus_2018 (accession no: MW018705) was found to be closely related to the strain previously isolated in different Egyptian governorates in 2017, and 2 strains were closely related to an isolate of equine origin. Electron microscopy examination of the skin lesions showed the presence of negatively stained rounded, non-enveloped virus particles with a size of 60 nm in diameter. In conclusion, continuous surveillance and characterization of the circulating strains using multiple sets of primers are important. Efficient biosecurity measures must be applied to decrease transmission of papillomavirus between the different animal species, especially in the mixed management system. [ABSTRACT FROM AUTHOR]

Background: Bovine papilloma is a neoplastic disease caused by bovine papillomaviruses (BPVs), which were recently divided into 5 genera and at least 24 genotypes. Objectives: The complete genome sequence of BPV type 15 (BPV Aks-02), a novel putative BPV type from skin samples from infected cows in Southern Xinjiang China, was determined by collecting warty lesions, followed by DNA extraction and amplicon sequencing. Methods: DNA was analyzed initially by polymerase chain reaction (PCR) using the degenerate primers FAP59 and FAP64. The complete genome sequences of the BPV Aks-02 were amplified by PCR using the amplification primers and sequencing primers. Sequence analysis and phylogenetic analysis were performed using bio-informatic software. Results: The nucleotide sequence of the L1 open reading frame (ORF) of BPV Aks-02 was 75% identity to the L1 ORF of BPV-9 reference strain from GenBank. The complete genome consisted of 7,189 base pairs (G + C content of 42.50%) that encoded 5 early (E8, E7, E1, E2, and E4) and 2 late (L1 and L2) genes. The E7 protein contained a consensus CX2CX29CX2C zinc-binding domain and a LxCxE motif. Among the different members of this group, the percentages of the complete genome and ORFs (including 5 early and 2 late ORFs) sequence identity of BPV Aks-02 were closer to the genus Xipapillomavirus 1 of the Xipapillomavirus genus. Phylogenetic analysis and sequence similarities based on the L1 ORF of BPV Aks-02 revealed the same cluster. Conclusions: The results suggest that BPV type (BPV Aks-02) clustered with members of the Xipapillomavirus genus as BPV 15 and were closely related to Xipapillomavirus 1. [ABSTRACT FROM AUTHOR]

Infection of bovine papillomavirus (BPV) has been associated with mucosal and/or cutaneous tumor development in bovids. To date, up to 27 genotypes of BPVs have been identified and classified based on the nucleotide sequence identity of L1 open reading frame. In the present study, the complete sequence of a novel BPV concurrently identified with BPV1 and BPV2 in the facial cutaneous papilloma lesion of a domestic cattle was characterized. The whole genome of the unclassified BPV was 7263 base pairs in full length with GC ratio of 42.9%. In comparison with published BPV sequences, L1 nucleotide sequence of the novel BPV shared 75% identity with BPV15, and was suggested to be classified in the genus, Xipapillomavirus. According to the criteria established by the International Committee on the Taxonomy of Viruses, the novel BPV was designated as BPV type 28. [ABSTRACT FROM AUTHOR]

Impaired keratinocyte differentiation has recently been suggested as a key event in equine hoof canker development. Koilocytotic appearance of keratinocytes, one of the most characteristic morphological alterations in hoof canker tissue, is also a common marker for papillomavirus (PV) infection, and bovine PV-1 and/or -2 (BPV-1/2) has previously been detected in equine canker patients. Therefore, the present study aimed to correlate the frequency and severity of koilocytotic keratinocytes with BPV detection in hoof canker samples. Hoof tissue of 5/18 canker-affected horses and 2/6 control horses tested positive for BPV-1/2 DNA using polymerase chain reaction. Thus, no association between the presence of BPV-1/2 papillomaviral DNA and koilocytotic appearance was found. Proteins associated with but not specific for PV infection were also investigated. Using immunohistochemistry, specific adhesion molecules (E-cadherin and β-catenin) and intermediate filaments (keratins 6 and 14) important for intact epidermal barrier function and keratinocyte differentiation were documented in control samples (n = 6) and in hoof canker tissue samples (n = 19). Altered expression patterns of intermediate filaments and adhesion molecules were demonstrated in canker tissue, confirming the importance of incomplete keratinocyte differentiation, as well as the crucial role of keratinocyte differentiation in hoof canker. [ABSTRACT FROM AUTHOR]

Prostate cancer is a candidate for immunotherapy because cancer cells express tissue-specific proteins that can be therapeutic targets. However, immune checkpoint inhibitors and active immunization have performed poorly in clinical trials. We developed a novel virus-like particle (VLP) vaccine composed of bovine papillomavirus L1 protein engineered to display surface docking sites. We decorated VLPs with peptides encoding T cell epitopes from two prostate cancer-associated tumor antigens, prostate stem cell antigen (PSCA), and prostatic acid phosphatase (PAP-1 and PAP-2), and a neo-antigen, stimulator of prostatic adenocarcinoma-specific T cells (SPAS-1). The VLP vaccines induced a mean frequency of antigen-specific IFN-γ secreting CD8 + T cells of 2.9% to PSCA, 9.5% to SPAS-1, 0.03% to PAP-1, and 0.03% to PAP-2 in tumor-bearing TRAMP mice. We treated TRAMP mice at 19–20 weeks of age, when mice have advanced stages of carcinogenesis, with either VLP vaccine, anti-PD1 antibody, or combination immunotherapy. The VLP vaccine alone or in combination with anti-PD1 antibody significantly reduced tumor burden, while anti-PD1 antibody had a modest non-significant therapeutic effect. All treatments significantly increased CD3 + and CD8 + T cell infiltration into tumor tissue compared to control mice, and combination therapy resulted in significantly greater CD3 + and CD8 + T cell infiltration than monotherapy. Reduction in tumor burden in vaccine-treated mice was inversely correlated with CD8 + T cell numbers in tumor tissue. No other immunotherapy has shown efficacy in this animal model of advanced prostate cancer, making bovine papillomavirus VLPs an attractive vaccine technology to test in patients with metastatic prostate cancer. [ABSTRACT FROM AUTHOR]

Equine sarcoids can be considered as the most common of the equine skin tumor types distributed worldwide which affects horses, donkeys and mules. The methods of transmission are environment contamination with successive trauma; skin infection direct or indirect transmissions from the affected animals; biting, rubbing, fomites or management practices and face flies. Dermatophytis, chronic skin rubbing, equine papilomatosis, squamous cell carcinoma, fibroma, fibrosarcoma, melanoma and granulation tissue are the common differential diagnoses of equine sarcoids. Bovine papillomavirus (BPV) is usually related to the equine sarcoids with the genetic, skin trauma and fly vectors that are characterized as possible factors of predisposing for disease development. Clinical examination, histopathology, detection of BPVDNA by PCR, electron microscope and immunohistochemistry are the diagnostic technique of equine sarcoid. The histopathological characteristics of sarcoids, have discovered that the classic epithelial variations in the hyperplasia, hyper-keratosis, picket fence, and elongated rete pegs. Treating equine sarcoids are difficult for veterinarians as a result of variable clinical presentation of lesions and frequent local recurrence cases. Each of the surgical and the non-surgical approaches are utilized to treat equine sarcoids with variable success rates. No existing approach of equine sarcoids' treatment has proven 100% efficient. Awareness enhancement to make equine owners, prevention of fly contact, use of breeding from those individuals thatare'immune', high geneti cresistance, early diagnosis and treatment of any confirmed lesions are the most valuable prevention methods for equine sarcoids. [ABSTRACT FROM AUTHOR]

Bovine papillomavirus proteins were extensively studied as a prototype for the human papillomavirus. Here, the crystal structure of the extended E2 DNA‐binding domain of the dominant transcription regulator from the bovine papillomavirus strain 1 is described in the space group P3121. We found two protein functional dimers packed in the asymmetric unit. This new protein arrangement inside the crystal led to the reduction of the mobility of a previously unobserved loop directly involved in the protein‐DNA interaction, which was then modeled for the first time. [ABSTRACT FROM AUTHOR]