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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 -
International Journal of Molecular... Jun 2023Safe and effective T cell vaccines are needed for the treatment or prevention of cancers as well as infectious agents where vaccines for neutralizing antibodies have... (Review)
Review
Safe and effective T cell vaccines are needed for the treatment or prevention of cancers as well as infectious agents where vaccines for neutralizing antibodies have performed poorly. Recent research highlights an important role for tissue-resident memory T cells (T cells) in protective immunity and the role of a subset of dendritic cells that are capable of cross-priming for the induction of T cells. However, efficient vaccine technologies that operate through cross-priming and induce robust CD8+ T cell responses are lacking. We developed a platform technology by genetically engineering the bovine papillomavirus L1 major capsid protein to insert a polyglutamic acid/cysteine motif in place of wild-type amino acids in the HI loop. Virus-like particles (VLPs) are formed by self-assembly in insect cells infected with a recombinant baculovirus. Polyarginine/cysteine-tagged antigens are linked to the VLP by a reversible disulfide bond. The VLP possesses self-adjuvanting properties due to the immunostimulatory activity of papillomavirus VLPs. Polyionic VLP vaccines induce robust CD8+ T cell responses in peripheral blood and tumor tissues. A prostate cancer polyionic VLP vaccine was more efficacious than other vaccines and immunotherapies for the treatment of prostate cancer in a physiologically relevant murine model and successfully treated more advanced diseases than the less efficacious technologies. The immunogenicity of polyionic VLP vaccines is dependent on particle size, reversible linkage of the antigen to the VLP, and an interferon type 1 and Toll-like receptor (TLR)3/7-dependent mechanism.
Topics: Male; Mice; Humans; Animals; Cross-Priming; Capsid Proteins; Cysteine; CD8-Positive T-Lymphocytes; Cancer Vaccines; Prostatic Neoplasms; Vaccines, Virus-Like Particle; Antibodies, Viral
PubMed: 37372999
DOI: 10.3390/ijms24129851 -
Viruses Sep 2023Equine 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...
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 , 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.
Topics: Animals; Horses; CRISPR-Cas Systems; Skin Neoplasms; Oncogenes; Fibroblasts; Gene Targeting
PubMed: 37766348
DOI: 10.3390/v15091942 -
Pathogens (Basel, Switzerland) Oct 2023Teat 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...
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.
PubMed: 38003743
DOI: 10.3390/pathogens12111278 -
Pathogens (Basel, Switzerland) Aug 2023Papillomas are benign epithelial lesions protruding on the epithelial surfaces as finger-like or warty projections. These lesions are often caused by papillomavirus (PV)...
Papillomas are benign epithelial lesions protruding on the epithelial surfaces as finger-like or warty projections. These lesions are often caused by papillomavirus (PV) infection. Congenital papillomas have been reported in foals. However, to date, no evidence of PV infection has been provided. In the present paper, we describe the main clinical-pathological features of a congenital papilloma observed in a foal. In addition, biomolecular tests demonstrated BPV1 infection in the case under study. Such data stimulate further investigations, even on archived samples, aiming to clarifying the etiology of equine congenital papilloma and the clinical relevance, if any, of BPV1 vertical transmission in horses.
PubMed: 37624019
DOI: 10.3390/pathogens12081059 -
Biomedicine & Pharmacotherapy =... Jan 2024The phosphatidyl inositol 3-kinase (PI3K)/AKT signaling plays a critical role in cancer cell proliferation, migration, and invasion. This signal transduction axis in...
The phosphatidyl inositol 3-kinase (PI3K)/AKT signaling plays a critical role in cancer cell proliferation, migration, and invasion. This signal transduction axis in HPV-positive cervical cancer has been proved to be directly activated by E6/E7 proteins of the virus enhancing cervical cancer progression. Hence, the PI3K/AKT pathway is one of the key therapeutic targets for HPV-positive cervical cancer. Here we discovered that oxyresveratrol (Oxy) at noncytotoxic concentration specifically suppressed the phosphorylation of AKT but not ERK1/2. This potent inhibitory effect of Oxy was still observed even when cells were stimulated with fetal bovine serum. Inhibition of AKT phosphorylation at serine 473 by Oxy resulted in a significant decrease in serine 9 phosphorylation of GSK-3β, a downstream target of AKT. Dephosphorylation of GSK-3β at this serine residue activates its function in promoting the degradation of MCL-1, an anti-apoptotic protein. Results clearly demonstrated that in association with GSK-3β activation, Oxy preferentially downregulated the expression of anti-apoptotic protein MCL-1. Furthermore, results from the functional analyses revealed that Oxy inhibited cervical cancer cell proliferation, at least in part through suppressing nuclear expression of Ki-67. Besides, the compound retarded cervical cancer cell migration even the cells were exposed to a potent enhancer of epithelial-mesenchymal transition, TGF-β1. In consistent with these data, Oxy reduced the expression of β-catenin, N-cadherin, and vimentin. In conclusion, the study disclosed that Oxy specifically inhibits the AKT/GSK-3β/MCL-1 axis resulting in reduction in cervical cancer cell viability, proliferation, and migration.
Topics: Female; Humans; Phosphatidylinositol 3-Kinase; Proto-Oncogene Proteins c-akt; Phosphatidylinositol 3-Kinases; Glycogen Synthase Kinase 3 beta; Uterine Cervical Neoplasms; Myeloid Cell Leukemia Sequence 1 Protein; Papillomavirus Infections; Signal Transduction; beta Catenin; Serine
PubMed: 38056236
DOI: 10.1016/j.biopha.2023.115982 -
Functional & Integrative Genomics Aug 2023Recent publications confirmed that long non-coding RNAs (lncRNAs) perform an essential function in gene-specific transcription regulation. Nevertheless, despite its...
Recent publications confirmed that long non-coding RNAs (lncRNAs) perform an essential function in gene-specific transcription regulation. Nevertheless, despite its important role, lncRNA has not yet been described in equine sarcoids, the skin neoplasia of horses. Therefore, the aim of this study is to deepen the knowledge about lncRNA expression in the pathogenesis of equine sarcoids and provide new insight into the regulatory function of lncRNA in the bovine papillomavirus-dependent neoplasia of horse dermal tissues. RNA sequencing (RNA-seq) data from 12 equine sarcoid samples and the corresponding controls were reanalyzed in this study. A total of 3396 differentially expressed (DE) lncRNAs and 128 DElncRNA-DE genes (DEGs) pairs were identified. Differentially expressed lncRNAs predicted target genes were enriched in pathways associated with inter alia the extracellular matrix disassembly and cancer pathways. Furthermore, methylation data from the same samples were integrated into the analysis, and 12 DElncRNAs were described as potentially disturbed by aberrant methylation. In conclusion, this study presents novel data about lncRNA's role in the pathogenesis of equine sarcoids.
Topics: Horses; Animals; RNA, Long Noncoding; Transcriptome; DNA Methylation; Epigenome; Skin Neoplasms
PubMed: 37552338
DOI: 10.1007/s10142-023-01200-2 -
Animals : An Open Access Journal From... Apr 2024Soft tissue tumors/sarcomas (STSs) in felines, encompassing a variety of mesenchymal tumors with similar histomorphological features, present diagnostic challenges due...
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.
PubMed: 38612342
DOI: 10.3390/ani14071103 -
Veterinary Pathology May 2024Sarcoids 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...
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 mm recurred, which was a significantly higher recurrence rate than that of sarcoids with an MC < 20, 8 of 44 cases recurred (18%), = .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%), < .001. In addition, univariate Cox regression analysis confirmed fibroblastic type and MC ≥ 20 as significant predictors for recurrence ( = .016 and = .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.
Topics: Horses; Horse Diseases; Animals; Neoplasm Recurrence, Local; Male; Female; Mitotic Index; Skin Neoplasms; Sarcoma
PubMed: 37937724
DOI: 10.1177/03009858231209408