Bovine Papillomavirus Research Articles

Structure-based virtual screening and drug repurposing studies indicate potential inhibitors of bovine papillomavirus E6 oncoprotein.

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.

A Combination of Chemotherapy and Autogenous Vaccine for Control of Bovine Papillomatosis in Cattle

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.

Bovine papillomavirus gene expression and inflammatory pathway activation vary between equine sarcoid tumour subtypes

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.

Molecular Detection by Rolling Circle Amplification Combined with Deep Sequencing of Mixed Infection by Bovine Papillomaviruses 2 and 4 in Carcinoma In Situ of the Bovine Esophageal Mucosa.

Papillomaviruses (PVs) are oncogenic and infect the skin and mucosa of various host species. Considering the recent advances in research on PVs using rolling circle amplification (RCA) followed by high-throughput sequencing (HTS), in this study, we aimed to investigate the bovine papillomavirus (BPV) types associated with proliferative lesions in the upper alimentary tract of an affected bull and characterize the viral strains through complete genome sequencing using this strategy. We analyzed the PV strains associated with two hyperplastic esophageal lesions through PCR using degenerate primer pairs and RCA, followed by HTS. HTS of the libraries generated using RCA products provided the whole genome sequence of BPV4 present in squamous papilloma, whereas the complete genome sequence of BPV2 and subgenomic fragments of BPV4 were identified in carcinoma in situ (CIS). For the first time, we have sequenced BPV2 identified from the CIS of the bovine upper alimentary canal. Additionally, RCA followed by HTS allowed characterization of the mixed infection by BPV2 and BPV4 in this lesion. These data reveal that BPV4 is not the only BPV type present in CIS of the esophageal mucous membrane; moreover, a mixed infection caused by BPV2 and BPV4 at the tested anatomical site was demonstrated.

Characterization of Bovine Papillomavirus Types Detected in Cattle Rumen Tissues from Amazon Region, Brazil.

The Bos Taurus Papillomavirus, commonly known as bovine papillomavirus (BPV), can cause lesions in the mucosa of the gastrointestinal tract (GIT) in cattle and induce the formation of papillomas in organs such as the pharynx, esophagus, rumen and reticulum. GIT papillomas can lead to feeding and breathing distress. Moreover, the sample collection is challenging, which reduces the BPV diagnosis in these organs. BPV can cause exophytic nodular, cauliflower-like, flat, filiform or atypical-shape papillomas at the epidermis. Histologically, the papillomas demonstrate orthokeratotic/parakeratotic hyperkeratosis and koilocytosis and, currently, BPV comprises 45 described types. The aim of this study was to carry out the genetic characterization of BPV present in rumen neoplastic lesions of cattle raised extensively in the Western Amazon region, Brazil. A total of 100 papillomatous ruminal samples were collected from animals slaughtered in Ji-Paraná and Urupá municipalities from the Rondônia state, Brazil. The samples were submitted to PCR using the primer pair FAP59/FAP64 and sequenced by the Sanger method. Histopathological analysis was performed on 24 samples, which had enough material for this purpose. As a result, samples were histologically classified as fibropapilloma and squamous papilloma. Among the samples analyzed, it was possible to identify the BPVs 2, 13 (Delta PVs) and 44, with one sample classified as a putative new subtype of BPV44. The present study could identify BPV13 and 44 types in cattle rumen tissues from the Brazilian Amazon region for the first time.

Molecular findings and virological assessment of bladder papillomavirus infection in cattle

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.

Molecular Characterization of the Presence of Bovine Papillomavirus in Cattle Teat Warts and a Different Treatment Approach

Background: Papillomatosis is a skin condition that is distinguished by benign proliferative tumors with a complicated etiology and epithelial proliferation. There is a need to perform a more thorough study on bovine papillomavirus and identify the virological properties of the agent in detail since a definitive treatment approach against this infection has not yet been completely identified and the suggested treatment outcomes differ. Methods: Samples were collected from warts developing on the teats of 500 cattle raised for milk production in Burdur Center and its districts. The samples were defrosted in order to extract DNA and the Dneasy Blood and Tissue Kit was used for the extraction procedure. By using a PCR assay, wart sample extracts were examined for 13 different BPV types (excluding BPV Type 7). For BPV type-specific primers, a protocol was utilized. Amplification products were demonstrated using agarose gel electrophoresis. Result: In the PCR test of 500 wart samples, BPV types (type 1-type 13) were detected in 378 (75.6%). In the general distribution of BPV types (single or mixed types) in teat warts, BPV-2 (n=85; 22.49%), BPV-8 (n=45; 11.90%), BPV-9 (n=48; 12.70%) and BPV-10 (n=52; 13.76%) were determined to be more common. In the study; it was determined that three different combined treatments provided 100% regression or complete recovery in warts developing on the teat of cattle. In conclusion; one of these three treatment combinations may be preferred for teat wart lesions in cattle.

Identifying regulatory elements and their RNA-binding proteins in the 3' untranslated regions of papillomavirus late mRNAs.

Human papillomaviruses (HPVs) infect cutaneous and mucosal epithelia to cause benign (warts) and malignant lesions (e.g. cervical cancer). Bovine papillomaviruses (BPVs) infect fibroblasts to cause fibropapillomas but can also infect cutaneous epithelial cells. For HPV-1, -16, -31 and BPV-1, cis-acting RNA elements in the late 3' untranslated region (3'UTR) control expression of virus proteins by binding host cell proteins. The present study compared the effects on gene expression of the cis-acting elements of seven PV late 3'UTRs (HPV-6b, -11, -16, -31 and BPV-1, -3 and -4) representing a range of different genera and species and pathological properties. pSV-beta-galactosidase reporter plasmids containing the late 3'UTRs from seven PVs were transiently transfected into cervical adenocarcinoma HeLa cells, and reporter gene expression quantified by reverse transcription-quantitative PCR and a beta-galactosidase assay. All elements inhibited gene expression in keratinocytes. Cancer-related types HPV-16 and -31, had the greatest inhibitory activity whereas the lowest inhibition was found in the non-cancer related types, BPV-3 and HPV-11. Using RBPmap version 1.1, bioinformatics predictions of factors binding the elements identified proteins which function mainly in mRNA splicing. Markedly, in terms of protein binding motifs, BPV late 3'UTR elements were similar to those of HPV-1a but not to other HPVs. Using HPV-1a as a model and siRNA depletion, the bioinformatics predictions were tested and it was found that PABPC4 was responsible for some of the 3'UTR repressive activity. The data revealed candidate proteins that could control PV late gene expression.

Management of cutaneous bovine papillomatosis in cross bred Holstein Friesian cow – Case Report

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-like-grown 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.

Bovine papillomavirus vertical transmission: BPV diversity and expression in maternal and fetal tissues.

Bovine Papillomaviruses (BPVs) constitute a diverse group within the Papillomaviridae family, playing a crucial role in bovine health and economic considerations. This study investigates the dynamics of vertical transmission of BPV in cattle, focusing on five cows and their reproductive tissues, as well as three gravid cows and their fetuses. DNA and RNA samples were extracted from the warts, fetal skin, placenta, uterus, ovary, and blood of cows, as well as the skin and blood of fetuses. Polymerase Chain Reaction (PCR) targeted BPV types 1-6 and 8-14, was assessed in both cows and fetuses. Additionally, Reverse Transcription PCR (RT-PCR) examined BPV-2 E5 oncogene expression in the skin and reproductive sites of mother cows and fetuses. Our findings unveil a rich diversity of BPV types, including BPV-2, 3, 9, 10, 12, and 14, present in both maternal and fetal tissues. Intriguingly, certain types, namely BPV-4, 6, 8, and 11, were exclusively identified in maternal tissues A higher diversity of BPVs was observed in cow warts, followed by cow blood, fetal blood, and fetal skin. Strikingly similar BPV types in gravid cow blood and fetuses suggest primary dissemination through the bloodstream and transmission via the placenta, though detected in lower numbers in cow uterus and ovary. Histopathological analysis revealed no abnormalities in the reproductive tissues despite the presence of BPV. However, in one bladder sample from a cow that did not consume bracken fern, urothelial neoplasia in situ was observed. The study extends beyond detection, exploring the expression of the BPV-2 E5 oncogene in fetal tissues, providing insights into potential cell implications. Comparative analyses with previous studies highlight the uniqueness of our investigation, encompassing a broader array of BPV types in the gravid cows and their fetuses. The findings not only establish a foundation for further investigations into the mechanisms of vertical transmission but also highlight the need for targeted interventions and surveillance strategies to mitigate potential health risks associated with specific BPV types.

Vertical Intrauterine Bovine and Ovine Papillomavirus Coinfection in Pregnant Cows.

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.

Phylogenetic analysis of papillomaviruses in dogs from southern Brazil: molecular epidemiology and investigation of mixed infections and spillover events.

Papillomaviruses (PVs) have been identified in several animal species, including dogs (canine papillomaviruses, CPVs) and cattle (bovine papillomaviruses, BPVs). Although some BPVs may occasionally infect species other than cattle, to the best of our knowledge, BPVs have not been reported in dogs to date. Herein, we carried out a retrospective phylogenetic study of PVs circulating in dogs from southern Brazil between 2017 and 2022, also investigating possible mixed infections and spillover events. For this, we screened 32 canine papilloma samples by PCR using the degenerate primers FAP59/64 and/or MY09/11, which amplify different regions of the L1 gene; the genomic target often used for PV classification/typing. Out these, 23 PV DNA samples were successfully amplified and sequenced. All PVs amplified by FAP59/64 (n = 22) were classified as CPV-1. On the other hand, PVs amplified by MY09/11 (n = 4) were classified as putative BPV-1. Among these, three samples showed mixed infection by CPV-1 and putative BPV-1. One of the putative BPV-1 detected in co-infected samples had the L1 gene full-sequenced, confirming the gene identity. Furthermore, the phylogenetic classifications from the FAP59/64 and/or MY09/11 amplicons were supported by a careful in silico analysis, which demonstrated that the analysis based on them matches to the classification from the complete L1 gene. Overall, we described CPV-1 circulation in southern Brazil over the years and thepotencial BPV infection in dogs (potential spillover event), as well as possible CPV/1/BPV-1 co-infections. Finally, we suggest the analysis of the complete genome of the putative BPVs detected in dogs in order to deepen the knowledge about the PV-host interactions.

A retrospective case series of the surgical management of thirty-one penile fibropapilloma cases presented to University College Dublin Veterinary Hospital (UCDVH) between 2017 and 2023

BackgroundPenile fibropapilloma is a condition caused by bovine papilloma virus and is frequently encountered in young bulls. Penile fibropapillomatosis is thought to be spread through homosexual mounting behaviour. Fibropapillomas of the penis are painful, often bleed and can impede normal intromission. Treatment may range from allowing time for slow, spontaneous regression to surgical resection but recurrence following surgery is reported by some authors.Case PresentationThirty one bulls that were presented to University College Dublin Veterinary Hospital from March 2017 to March 2023 for surgical resection of penile fibropapillomas were included in this retrospective case series. Twenty-seven of the 31 bulls (87%) were under two years of age. The majority (42%) of bulls presented were Hereford, but Angus, Charolais, Holstein-Friesian and Limousin breeds were also seen. Following examination and diagnosis of penile fibropapilloma, regional anaesthesia (xylazine-procaine epidural and internal pudendal nerve block) and standing surgical intervention (resection and cautery) was performed in each case. Phone call follow-up was performed by one author (EET) in all 31 cases and 2 cases out of the 28 that were contactable showed post-surgical recurrence of penile fibropapillomatosis (i.e., 7.1% recurrence rate).ConclusionThis case series summarises the history and presenting findings of 31 bovine penile fibropapilloma cases and describes a regional anaesthetic and standing surgical approach for successful case management.

Feline Facial Spindle Cell Tumors in 29 Cats: Histomorphological and Immunohistochemical Characterization.

Soft tissue tumors/sarcomas (STSs) in felines, encompassing a variety of mesenchymal tumors with similar histomorphological features, present diagnostic challenges due to their diverse cellular origins and the overlap with other tumor types such as feline sarcoid. This study aimed to delineate the clinical, histomorphological, and immunohistochemical characteristics of 34 feline facial spindle cell tumors affecting 29 cats, including testing for bovine papillomavirus type 14 (BPV14), the virus causing feline sarcoids. Only five out of 12 tumors previously diagnosed as feline sarcoids based on histomorphology were confirmed by PCR for BPV14, underscoring the importance of comprehensive diagnostic approaches to accurately distinguish between STSs and feline sarcoids. This study shows that most facial spindle cell tumors were compatible with peripheral nerve sheath tumors (PNSTs) based on positive immunohistochemical staining for Sox10 and other immunohistochemical markers such as GFAP, NSE, and S100. Some of these tumors displayed as multiple independent masses on the face or as erosive and ulcerative lesions without obvious mass formation, an atypical presentation and an important highlight for general practitioners, dermatologists, and oncologists. This study also describes periadnexal whorling of neoplastic cells as a novel histomorphologic finding in feline facial PNSTs and emphasizes Sox10 as a useful complementary immunohistochemical marker for the diagnosis of facial PNST in cats, providing valuable insights for veterinary pathologists.

The possible role of haematophagous flies in the incidence of bovine teat papillomatosis.

The relationship between the incidence of bovine teat papillomatosis and the activity of haematophagous flies was investigated in Japan. A total of 15,737 flies consisting of 33 species were collected by dry ice-baited mosquito net (DMN) trap and a sweep net from udders of cattle. Simulium aokii (Takahasi) of Simuliidae (black flies) was the predominant species, followed by S. tobetsuense Ono and S. iwatense (Shiraki). Simulium aokii had the highest peak in October, followed by September. Numbers of blood spots from the bites per teat in nulliparous cattle were significantly correlated with numbers of S. aokii collected by DMN trap. Numbers of teats with warts and spots of blood from the bites per teat were significantly more abundant in anterior teats than posterior teats. The average incidence of teat papillomatosis in nulliparous cattle was significantly higher than that in parous cattle, and the highest incidence by month was in May, followed by April. Although bovine papillomavirus (BPV) DNA was not detected in flies examined, the presence of black flies and blood spots from their bites were associated with subsequent high incidence of growing warts. In particular, it would pay to give attention to species such as S. aokii that severely attack udders in the present locality. Further investigations for the detection of BPV DNA from flies parasitizing on teats are needed.

Investigation of the Presence of Bovine Papillomavirus in Blood Leukocytes of Cattle in West Mediterranean of Turkey

One hundred Holstein cattle, varying in age from one to ten years, who had warts on different parts of its bodies and had previously had Bovine papillomavirus (BPV) typing had blood samples taken from them from various managements in Burdur-Center and its surroundings. DNA was extracted from leukocytes using the DNeasy Blood & Tissue Kit (Qiagen, Germany). RT-PCR test was performed using consensus and type-specific primers for the detection of BPV types. As a result of the study, RT-PCR test and consensus primers were not detected in blood leukocyte samples. Through the use of type-specific primers in an RT-PCR assay, the viral genome components of BPV-10 (56), BPV-11 (1), BPV-10+BPV-11 (2), BPV-10+BPV-12, and BPV-10+BPV-14 (2) were detected in these samples. BPV-12 was detected for the first time in blood leucocytes. In blood samples taken from animals classified according to the anatomical regions where the warts are located the highest BPV positivity (22,2%) was detected in animals with warts on the teats. Also, the most BPV-10 type was determined in the blood samples of animals with wart lesions on the teat and lobes. When the distribution of BPV PCR positive samples according to age groups was made, BPV PCR positive was found mostly in the between 1 and 47 month age group (71,4%). It was determined that the prevalence of BPV was high in the between 1 and 47 age group, while the rates of 48-83 months and later decreased with increasing age. In this investigation, it was found that BPV type 10 had been prevalent in blood leukocyte samples from cattle with warts in various areas of the body and with variable macroscopic appearance.

Molecular Detection and Quantification of Ovine Papillomavirus DNA in Equine Sarcoid

Equine sarcoids are caused by infection with bovine papillomavirus (BPV) types 1, 2, and possibly 13. However, a number of sarcoids lack BPV DNA, and new potential etiological agents for sarcoid diseases need to be considered. High-performance digital droplet polymerase chain reaction (ddPCR) was used for the quantitative detection of ovine papillomavirus (OaPV) types 1–4 DNA from 63 sarcoid DNA samples collected in Austria. All samples were comparatively evaluated for OaPV DNA loads by qPCR. Conventional PCR and amplicon sequencing were used to validate the data. Of the 63 sarcoid DNA isolates, ddPCR was able to detect 22 samples harboring OaPV DNA (34.92%), whereas only five of the OaPV-positive samples were revealed by qPCR (22.72%). The differences in detection by ddPCR and qPCR were statistically significant (p<0.05). The detected OaPV types were OaPV1, 3, and 4. Both methods failed to detect OaPV2 DNA, which could be due to the limited number of examined samples. Importantly, ddPCR detected multiple types of OaPV DNA in seven cases, whereas the qPCR failed to detect multiple infections. This study is the first to provide evidence of the presence of OaPV types 1, 3, and 4 DNA in a subset of equine sarcoids. The comparative detection approach underscores the superior sensitivity of ddPCR compared to that of qPCR.

Comparative structural studies on Bovine papillomavirus E6 oncoproteins: Novel insights into viral infection and cell transformation from homology modeling and molecular dynamics simulations.

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.

Comprehensive Network and Structural Analysis of Bovine Papillomavirus, Squamous Cell Carcinoma Markers, and Elucidation of Efficacy Mechanisms of Phytochemicals from Thuja Occidentalis

Papillomaviruses infect cutaneous tissue in various species including bovines and from benign warts to malignant squamous cell carcinoma causing severe economic losses to the farmers. The mechanisms by which bovine papillomaviruses interact with host tissue are unclear. Hence in this study using classical network analysis tools, we evaluated interactions of Bovine papilloma (BPV) variants, with markers and receptors implicated in squamous cell carcinoma. Additionally, the Thuja phytoconstituents were also evaluated for its potential to target the BPV and squamous cell carcinoma network interactions to understand the mechanism of its clinical benefits. Various protein composition of 14 different virus variants of BPV were assessed against 24 markers of squamous cell carcinoma. Among these interactions EGFR consistently exhibited high-affinity interactions with the E1 protein in all isoforms of BPV. Type 4 BPV displayed the maximum number of binding sites (14) with a binding pocket score ranging from 15.47 to 141.34 and a probability score of 0.75 to 0.99. The comparison of the binding pockets identified that BPV types 2 and 13 had the highest number of common amino acid sequences. Further the alpha helix structure of specific common amino acid sequences contributes to a more robust and widespread affinity interaction with both E1 of various BPV types and EGFR. Analysis of Thuja phytochemicals suggested superior efficacy of Beyerene and Terpinene-4-ol towards all ten BPV targets and bEGFR. In conclusion, our comprehensive study leading to identification of E1 protein of BPV as a major interacting network with bEGFR, their key binding sites, and efficacy of Thuja phytoconstituents offer valuable insight into further experimental validation and development of novel therapeutic strategies against BPV-associated diseases.

Abortion storm of Yili horses is associated with Equus caballus papillomavirus 2 variant infection.

Nine different species of Equus caballus papillomavirus (EcPV) and three bovine papillomaviruses (BPVs) have been reported to infect horses. However, there are few descriptions of such infections in China. In our pioneer study on Chinese horses, we identified EcPV-2 in the nasal swabs (4/230, 1.7%) of Yili horses, and the semen (3/18, 16.7%) of thoroughbred horses. This indicated that EcPV is indeed hosted by horses in China, and that EcPV-2 might be transmitted though breeding. Further detection of EcPVs in the lung tissues of aborted fetuses of Yili horses, which were originally negative for equid herpes viruses, demonstrated EcPV-2 positivity in 19 of 50 samples, thereby indicating that EcPV-2 may be a new pathogen responsible for causing abortion. Thereafter, sequence analyses of the L1 genes of 26 EcPV-2 in China were performed, indicating that EcPV-2, which primarily infects horses in China, shared 98.3-99.9% nt identity with the published sequences for EcPV-2. These observations indicated that EcPV-2 identified in the current study were highly similar variants of the previously identified strains of EcPV-2. Phylogenetic analysis based on L1 gene sequences from GenBank showed that the EcPV-2 found in Chinese horses was closely related to and clustered together with an already known EcPV-2a lineage. Our study provides the first evidence related to EcPV-2 infection in Chinese horses, which can serve as a causative agent for Yili horse abortions, and may thus lay the foundation for a systematic and detailed epidemiological study of this infection in Chinese horses.