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Veterinary Microbiology Feb 2024The family Papillomaviridae includes a plethora of viral species infecting virtually all vertebrates excluding amphibians, with astonishing impact on human and animal... (Review)
Review
The family Papillomaviridae includes a plethora of viral species infecting virtually all vertebrates excluding amphibians, with astonishing impact on human and animal health. Although more than 250 species have been described in humans, the total number of papillomaviruses (PVs) discovered in animals does not reach up to this number. In animals, PV infections are mostly asymptomatic or can cause variable clinical conditions ranging from self-limiting papillomas and other cutaneous and mucosal benign lesions to cancer. Most of animal PV types have been discovered in cattle, dogs, horses, and cats with other farm host species remaining overlooked. In particular, the number of PV types so far identified in sheep is limited. This paper comprehensively reviews ovine PVs features, including viral taxonomy and evolution; genome organization; viral tropism and pathogenesis; macroscopical features and histopathological patterns, as well as available diagnostics tools. Data are critically presented and discussed in terms of impact on veterinary and public health. The development of future dedicated research is also discussed.
Topics: Animals; Deltapapillomavirus; Papilloma; Papillomaviridae; Papillomavirus Infections; Sheep; Sheep Diseases; Virulence
PubMed: 38160507
DOI: 10.1016/j.vetmic.2023.109955 -
Brazilian Journal of Microbiology :... Mar 2020Thirty-one bovine cutaneous warts were submitted to macroscopic and histological analyses and to molecular analyses to partial amplification and sequencing of the L1...
Thirty-one bovine cutaneous warts were submitted to macroscopic and histological analyses and to molecular analyses to partial amplification and sequencing of the L1 gene of bovine papillomavirus (BPV). Viral types detected were BPV1 (52%), BPV2 (29%), BPV6 (16%) and BPV10 (3%). BPV2 had lower frequency in papilloma in comparison to that in fibropapilloma (p = 0.002).
Topics: Animals; Bovine papillomavirus 1; Cattle; Cattle Diseases; DNA, Viral; Papilloma; Papillomaviridae; Papillomavirus Infections; Skin; Warts
PubMed: 31388938
DOI: 10.1007/s42770-019-00121-2 -
Veterinary Immunology and... Feb 2000Papillomaviruses are species- and tissue-specific double-stranded DNA viruses. These viruses cause epithelial tumours in many animals, including man. Typically, the... (Review)
Review
Papillomaviruses are species- and tissue-specific double-stranded DNA viruses. These viruses cause epithelial tumours in many animals, including man. Typically, the benign warts undergo spontaneous, immune-mediated regression, most likely effected by T-cells (especially CD4, but also CD8 subsets), whereas humoral immunity can prevent new infections. Some papillomavirus infections fail to regress spontaneously and others progress to malignant epithelial tumours. Additionally, the impact of these lesions is greater in immunosuppressed individuals. Many therapies are ineffective, and there is much interest in the potential for immunological intervention in papillomavirus infections of man and animals. Vaccination can be achieved with 'live' virus, formalin-inactivated virus, synthetic virus-like particles, and DNA vaccination. There has been much recent progress in the development of such vaccines for papillomavirus infections in the rabbit, ox and dog. Success in these animal models suggests that similar approaches may prove useful for prophylactic or therapeutic vaccination against the important human papillomaviruses involved in the development of cutaneous and anogenital warts, laryngeal papillomatosis, and cervical cancer.
Topics: Animals; Antibodies, Viral; Cattle; Disease Models, Animal; Dogs; Humans; Immunity, Cellular; Mouth Neoplasms; Papillomaviridae; Papillomavirus Infections; Rabbits; Skin Neoplasms; Tumor Virus Infections; Viral Vaccines; Warts
PubMed: 10690928
DOI: 10.1016/s0165-2427(99)00165-8 -
Journal of Virological Methods Nov 2014The bovine papillomavirus (BPV) is the etiological agent of bovine papillomatosis, which causes significant economic losses to livestock, characterized by the presence...
The bovine papillomavirus (BPV) is the etiological agent of bovine papillomatosis, which causes significant economic losses to livestock, characterized by the presence of papillomas that regress spontaneously or persist and progress to malignancy. Currently, there are 13 types of BPVs described in the literature as well as 32 putative new types. This study aimed to isolate viral particles of BPV from skin papillomas, using a novel viral isolation method. The virus types were previously identified with new primers designed. 77 cutaneous papilloma samples of 27 animals, Simmental breed, were surgically removed. The DNA was extracted and subjected to PCR using Delta-Epsilon and Xi primers. The bands were purified and sequenced. The sequences were analyzed using software and compared to the GenBank database, by BLAST tool. The viral typing showed a prevalence of BPV-2 in 81.81% of samples. It was also detected the presence of the putative new virus type BR/UEL2 in one sample. Virus isolation was performed by ultracentrifugation in a single density of cesium chloride. The method of virus isolation is less laborious than those previously described, allowing the isolation of complete virus particles of BPV-2.
Topics: Animals; Cattle; Cattle Diseases; DNA, Viral; Papillomaviridae; Papillomavirus Infections; Polymerase Chain Reaction; Sequence Analysis, DNA; Skin; Ultracentrifugation; Virion; Virology
PubMed: 25102429
DOI: 10.1016/j.jviromet.2014.07.029 -
Microbiological Reviews Jun 1982
Review
Topics: Animals; Antigens, Viral; Biological Evolution; Bovine papillomavirus 1; Cell Transformation, Viral; Cells, Cultured; Cottontail rabbit papillomavirus; Genes, Viral; Humans; Papilloma; Papillomaviridae; Recombination, Genetic; Transcription, Genetic; Tumor Virus Infections
PubMed: 6289064
DOI: 10.1128/mr.46.2.191-207.1982 -
Genetics and Molecular Research : GMR Oct 2015The bovine papillomavirus (BPV) causes papillomas that regress spontaneously, but can also progress to malignancy. This study evaluated the role of BPV in oncogenesis....
The bovine papillomavirus (BPV) causes papillomas that regress spontaneously, but can also progress to malignancy. This study evaluated the role of BPV in oncogenesis. Twenty-four samples from uninfected calves and the papillomas of BPV infected cattle were subjected to molecular diagnosis, as well as histopathological and immunohistochemical analyses. The comet assay (CA) was used to evaluate the clastogenic potential of BPV. The results confirmed the presence of BPV-2, 3, 5, and 9 in infected samples. Histopathological analysis revealed acanthosis, koilocytosis, hypergranulosis, hyperkeratosis, and transformed fibroblasts.E7 and L1 BPV proteins were detected in the epithelium, as well as in the connective tissues, indicating productive infection at different sites. CA results showed that BPV-2, 5, and 9 exhibit the same level of clastogenicity. These findings support the oncogenic action of BPV in establishing a favorable microenvironment for oncogenesis.
Topics: Animals; Bovine papillomavirus 1; Carcinogenesis; Cattle; Cattle Diseases; Comet Assay; DNA, Viral; Papillomaviridae; Papillomavirus Infections
PubMed: 26505447
DOI: 10.4238/2015.October.21.15 -
Journal of Virology Jan 2017Papillomaviruses are small, double-stranded DNA viruses that encode the E2 protein, which controls transcription, replication, and genome maintenance in infected cells....
UNLABELLED
Papillomaviruses are small, double-stranded DNA viruses that encode the E2 protein, which controls transcription, replication, and genome maintenance in infected cells. Posttranslational modifications (PTMs) affecting E2 function and stability have been demonstrated for multiple types of papillomaviruses. Here we describe the first phosphorylation event involving a conserved tyrosine (Y) in the bovine papillomavirus 1 (BPV-1) E2 protein at amino acid 102. While its phosphodeficient phenylalanine (F) mutant activated both transcription and replication in luciferase reporter assays, a mutant that may act as a phosphomimetic, with a Y102-to-glutamate (E) mutation, lost both activities. The E2 Y102F protein interacted with cellular E2-binding factors and the viral helicase E1; however, in contrast, the Y102E mutant associated with only a subset and was unable to bind to E1. While the Y102F mutant fully supported transient viral DNA replication, BPV genomes encoding this mutation as well as Y102E were not maintained as stable episomes in murine C127 cells. These data imply that phosphorylation at Y102 disrupts the helical fold of the N-terminal region of E2 and its interaction with key cellular and viral proteins. We hypothesize that the resulting inhibition of viral transcription and replication in basal epithelial cells prevents the development of a lytic infection.
IMPORTANCE
Papillomaviruses (PVs) are small, double-stranded DNA viruses that are responsible for cervical, oropharyngeal, and various genitourinary cancers. Although vaccines against the major oncogenic human PVs are available, there is no effective treatment for existing infections. One approach to better understand the viral replicative cycle, and potential therapies to target it, is to examine the posttranslational modification of viral proteins and its effect on function. Here we have discovered that the bovine papillomavirus 1 (BPV-1) transcription and replication regulator E2 is phosphorylated at residue Y102. While a phosphodeficient mutant at this site was fully functional, a phosphomimetic mutant displayed impaired transcription and replication activity as well as a lack of an association with certain E2-binding proteins. This study highlights the influence of posttranslational modifications on viral protein function and provides additional insight into the complex interplay between papillomaviruses and their hosts.
Topics: Alphapapillomavirus; Animals; Bovine papillomavirus 1; Cattle; DNA-Binding Proteins; Gene Expression Regulation, Viral; Genome, Viral; Humans; Models, Molecular; Mutation; Phosphorylation; Plasmids; Protein Conformation; Protein Transport; Transcription, Genetic; Tyrosine; Viral Proteins; Virus Replication
PubMed: 27807239
DOI: 10.1128/JVI.01854-16 -
Virology Nov 2022Animal models are necessary to study how cutaneous human papillomaviruses (HPVs) are associated with carcinogenesis. The cottontail rabbit papillomavirus (CRPV) induces...
Animal models are necessary to study how cutaneous human papillomaviruses (HPVs) are associated with carcinogenesis. The cottontail rabbit papillomavirus (CRPV) induces papilloma in the -cutaneous skin of rabbits and serves as an established animal model for HPVlinked carcinogenesis where viral E6 proteins play crucial roles. Several studies have reported the dysregulation of the Notch signaling pathway by cutaneous beta HPV, bovine PV and mouse PV E6 via their association with Mastermind-like 1 protein (MAML1), thus interfering with cell proliferation and differentiation. However, the CRPV E6 gene encodes an elongated E6 protein (long E6, LE6) and an N-terminally truncated product (short E6, SE6) making it unique from other E6 proteins. Here, we describe the interaction between both CRPV E6 proteins and MAML1 and their ability to downregulate the Notch signaling pathway which could be a way CRPV infection induces carcinogenesis similar to beta HPV.
Topics: Humans; Rabbits; Animals; Cattle; Mice; Cottontail rabbit papillomavirus; Papillomavirus Infections; Papillomaviridae; Signal Transduction; Carcinogenesis; DNA-Binding Proteins; Transcription Factors
PubMed: 36155393
DOI: 10.1016/j.virol.2022.08.014 -
Virus Research Apr 2023Bladder tumors of cattle are very uncommon accounting from 0.1% to 0.01% of all bovine malignancies. Bladder tumors are common in cattle grazing on bracken fern-infested... (Review)
Review
INTRODUCTION
Bladder tumors of cattle are very uncommon accounting from 0.1% to 0.01% of all bovine malignancies. Bladder tumors are common in cattle grazing on bracken fern-infested pasturelands. Bovine papillomaviruses have a crucial role in tumors of bovine urinary bladder.
AIM OF THE STUDY
To investigate the potential association of ovine papillomavirus (OaPV) infection with bladder carcinogenesis of cattle.
METHODS
Droplet digital PCR was used to detect and quantify the nucleic acids of OaPVs in bladder tumors of cattle that were collected at public and private slaughterhouses.
RESULTS
OaPV DNA and RNA were detected and quantified in 10 bladder tumors of cattle that were tested negative for bovine papillomaviruses. The most prevalent genotypes were OaPV1 and OaPV2. OaPV4 was rarely observed. Furthermore, we detected a significant overexpression and hyperphosphorylation of pRb and a significant overexpression and activation of the calpain-1 as well as a significant overexpression of E2F3 and of phosphorylated (activated) PDGFβR in neoplastic bladders in comparison with healthy bladders, which suggests that E2F3 and PDGFβR may play an important role in OaPV-mediated molecular pathways that lead to bladder carcinogenesis.
CONCLUSION
In all tumors, OaPV RNA could explain the causality of the disease of the urinary bladder. Therefore, persistent infections by OaPVs could be involved in bladder carcinogenesis. Our data showed that there is a possible etiologic association of OaPVs with bladder tumors of cattle.
Topics: Animals; Cattle; Sheep; Bovine papillomavirus 1; Urinary Bladder Neoplasms; Urinary Bladder; Polymerase Chain Reaction; Carcinogenesis; Cattle Diseases; Papillomavirus Infections
PubMed: 36878382
DOI: 10.1016/j.virusres.2023.199084 -
Frontiers in Immunology 2022Persistent infection and tumorigenesis by papillomaviruses (PVs) require viral manipulation of various cellular processes, including those involved in innate immune...
Persistent infection and tumorigenesis by papillomaviruses (PVs) require viral manipulation of various cellular processes, including those involved in innate immune responses. The cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes (cGAS-STING) pathway has emerged as an essential innate immune sensing system, that recognizes DNA and trigger potent antiviral effector responses. In this study, we found that bovine PV (BPV) E5 protein, the major oncoprotein of bovine delta PVs, interacts with STING but not with cGAS in a spontaneous BPV infection of neoplastic urothelial cells of cattle. Real-time RT-PCR revealed a significant reduction in both cGAS and STING transcripts in E5-expressing cells. Furthermore, western blot (WB) analysis failed to detect any variation in the expression of interferon-inducible protein 16 (IFI16), an upstream effector of the STING pathway. A ternary complex composed of E5/STING/IFI16 was also observed. Co-immunoprecipitation studies showed that STING interacts with a protein network composed of total and phosphorylated TANK-binding kinase 1 (TBK1), total and phosphorylated interferon regulatory factor 3 (IRF3), IRF7, IKKα, IKKβ, IKKϵ, ELKS, MEKK3, and TAK1. RT-qPCR revealed a significant reduction in TBK1 mRNA levels in BPV-infected cells. WB analysis revealed significantly reduced expression levels of pTBK1, which is essential for the activation and phosphorylation of IRF3, a prerequisite for the latter to enter the nucleus to activate type 1 IFN genes. WB also revealed significantly down-expression of IKKα, IKKβ, IKKϵ, and overexpression of IRF7, ELKS, MEKK3, and TAK1in BPV-positive urothelial cells compared with that in uninfected healthy cells. Phosphorylated p65 (p-p65) was significantly reduced in both the nuclear and cytosolic compartments of BPV-infected cells compared with that in uninfected urothelial cells. Our results suggest that the innate immune signaling pathway mediated by cGAS-STING is impaired in cells infected with BPV. Therefore, effective immune responses are not elicited against these viruses, which facilitates persistent viral infection and subsequent tumorigenesis.
Topics: Cattle; Animals; I-kappa B Kinase; Membrane Proteins; Nucleotidyltransferases; Signal Transduction; Papillomaviridae; Virus Diseases; Oncogene Proteins; Carcinogenesis; Interferons
PubMed: 36311756
DOI: 10.3389/fimmu.2022.937736