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19 pages, 4544 KiB

Open AccessArticle

Novel Production of Bovine Papillomavirus Pseudovirions in Tobacco Plants

by Inge Pietersen, Albertha van Zyl, Edward Rybicki and Inga Hitzeroth

Pathogens 2020, 9(12), 996; https://doi.org/10.3390/pathogens9120996 - 28 Nov 2020

Viewed by 2560

Abstract

Vaccine efficacy requires the production of neutralising antibodies which offer protection against the native virus. The current gold standard for determining the presence of neutralising antibodies is the pseudovirion-based neutralisation assay (PBNA). PBNAs utilise pseudovirions (PsVs), structures which mimic native virus capsids, but [...] Read more.

Vaccine efficacy requires the production of neutralising antibodies which offer protection against the native virus. The current gold standard for determining the presence of neutralising antibodies is the pseudovirion-based neutralisation assay (PBNA). PBNAs utilise pseudovirions (PsVs), structures which mimic native virus capsids, but contain non-viral nucleic material. PsVs are currently produced in expensive cell culture systems, which limits their production, yet plant expression systems may offer cheaper, safer alternatives. Our aim was to determine whether plants could be used for the production of functional PsVs of bovine papillomavirus 1 (BPV1), an important causative agent of economically damaging bovine papillomas in cattle and equine sarcoids in horses and wild equids. BPV1 capsid proteins, L1 and L2, and a self-replicating reporter plasmid were transiently expressed in Nicotiana benthamiana to produce virus-like particles (VLPs) and PsVs. Strategies to enhance particle yields were investigated and optimised protocols were established. The PsVs’ ability to infect mammalian cells and express their encapsidated reporter genes in vitro was confirmed, and their functionality as reagents in PBNAs was demonstrated through their neutralisation by several different antibodies. This is the first report of BPV PsVs expressed in plants and demonstrates the potential for the development of therapeutic veterinary vaccines in planta. Full article

(This article belongs to the Special Issue Bovine Papillomavirus Infection)

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12 pages, 1721 KiB

Open AccessArticle

High Genotypic Diversity, Putative New Types and Intra-Genotype Variants of Bovine Papillomavirus in Northeast Brazil

by Rebeca P. Figueirêdo, Gabriela F. Santos, Luana B. Oliveira, Lucas A. B. O. Santos, Débora M. Barreto, Alexandre L. Cândido, Ana C. Campos, Edisio O. Azevedo and Marcus V. A. Batista

Pathogens 2020, 9(9), 748; https://doi.org/10.3390/pathogens9090748 - 15 Sep 2020

Cited by 7 | Viewed by 2365

Abstract

Bovine papillomavirus (BPV) can cause damage to the epithelial and mucosal tissue and currently presents 28 known types. Not all BPV types are associated with the development of cancer in cattle. Studies have shown that variants of human papillomavirus types can present different [...] Read more.

Bovine papillomavirus (BPV) can cause damage to the epithelial and mucosal tissue and currently presents 28 known types. Not all BPV types are associated with the development of cancer in cattle. Studies have shown that variants of human papillomavirus types can present different pathogenic profiles. However, despite the similarity, it is not yet known whether variants of BPV types can also present varying degrees of pathogenicity. Thus, the aim of this study was to evaluate the genetic variability of BPV types and variants isolated in Northeastern Brazil. Samples were obtained from animals with papillomatous lesions. BPV DNA was detected by the amplification of the L1 gene and genotyping was performed by sequencing. Mutations were analyzed in a phylogenetic, structural and functional context. In total, 52 positive samples were obtained and 11 different BPV types were identified in the samples. Ten putative new BPV types were also identified. In addition, several non-synonymous mutations were identified and predicted to alter protein stability, having an impact on immune evasion. The study demonstrated a high genetic diversity of BPV in the region with a large number of mutations identified, serving as a basis for more efficient control measures to be adopted for bovine papillomatosis. Full article

(This article belongs to the Special Issue Bovine Papillomavirus Infection)

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19 pages, 5852 KiB

Open AccessArticle

Prohibitin 2 is Involved in Parkin-Mediated Mitophagy in Urothelial Cells of Cattle Infected with Bovine Papillomavirus

by Francesca De Falco, Ivan Gentile, Pellegrino Cerino, Anna Cutarelli, Cornel Catoi and Sante Roperto

Pathogens 2020, 9(8), 621; https://doi.org/10.3390/pathogens9080621 - 29 Jul 2020

Cited by 9 | Viewed by 2784

Abstract

Prohibitin 2 (PHB2), an inner mitochondrial membrane (IMM) protein, has recently been identified as a novel receptor involved in parkin-mediated mitophagy. In the field of veterinary medicine, the role of PHB2 in parkin-mediated mitophagy was described, for the first time, in urothelial cells [...] Read more.

Prohibitin 2 (PHB2), an inner mitochondrial membrane (IMM) protein, has recently been identified as a novel receptor involved in parkin-mediated mitophagy. In the field of veterinary medicine, the role of PHB2 in parkin-mediated mitophagy was described, for the first time, in urothelial cells of cattle, naturally infected with bovine papillomavirus (BPV). The BPV2 and BPV13 E5 oncoprotein, responsible for abortive infections in urothelial cells, was detected by RT-PCR. Severe ultrastructural abnormalities of the inner mitochondrial membrane were detected using transmission electron microscopy. PHB2 formed a functional complex with PHB1. PHB2 was significantly overexpressed in mitochondrial fractions from urothelial mucosa samples taken from cattle harbouring BPV infection. PHB2 overexpression could be attributed to mitochondrial dysfunction, as its expression levels in the cytosolic, microsomal, and nuclear fractions were seen to be unmodified. Immunoprecipitation studies revealed the interaction between PHB2 and phosphorylated forms of both PINK1 and parkin. Furthermore, PHB2 interacted with LC3-II, a marker of autophagosomal membranes and autophagy receptors, such as p62 and optineurin. PHB2 was shown to interact with transcription factor EB (TFEB), which is activated following parkin-mediated mitophagy, and embryonic stem cell-expressed Ras (ERAS), a constitutive protein coded by ERas. Western blot analysis revealed a significant overexpression of unphosphorylated TFEB in mitochondrial and nuclear fractions from urothelial mucosa samples from cattle suffering from BPV infection. Finally, PHB2 interacted with ERAS, believed to be involved in mitophagosome maturation. Taken together, the molecular and ultrastructural findings of this study suggested that BPV infection is responsible for parkin-dependent mitophagy, in the pathway of which PHB2 plays a crucial role. Full article

(This article belongs to the Special Issue Bovine Papillomavirus Infection)

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9 pages, 1112 KiB

Open AccessArticle

Bovine Papillomavirus 1 Gets Out of the Flock: Detection in an Ovine Wart in Sicily

by Federica Savini, Laura Gallina, Alice Prosperi, Roberto Puleio, Antonio Lavazza, Patrizia Di Marco, Serena Tumino, Ana Moreno, Davide Lelli, Annalisa Guercio and Alessandra Scagliarini

Pathogens 2020, 9(6), 429; https://doi.org/10.3390/pathogens9060429 - 30 May 2020

Cited by 9 | Viewed by 2590

Abstract

A proliferative cauliflower lesion was excised from the udder of a sheep. Histological investigation confirmed the macroscopic classification of the lesion as a papilloma, without any fibroblastic proliferation. PCR revealed the presence of bovine papillomavirus (BPV), which was further confirmed by the identification [...] Read more.

A proliferative cauliflower lesion was excised from the udder of a sheep. Histological investigation confirmed the macroscopic classification of the lesion as a papilloma, without any fibroblastic proliferation. PCR revealed the presence of bovine papillomavirus (BPV), which was further confirmed by the identification of a Deltapapillomavirus 4 by Next Generation Sequencing analysis. This was subsequently classified as bovine papillomavirus type 1. Negative staining electron microscopy (EM) analyses produced negative test results for papillomavirus particles. RNA in situ hybridization (ISH) confirmed the presence of BPV-1. The results further confirm the ability of BPVs belonging to the Deltapapillomavirus genus to infect distantly related species and to cause lesions that are different from sarcoids. Full article

(This article belongs to the Special Issue Bovine Papillomavirus Infection)

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15 pages, 7667 KiB

Open AccessArticle

Bovine Papillomavirus Type 2 Infection Associated with Papillomatosis of the Amniotic Membrane in Water Buffaloes (Bubalus bubalis)

by Valeria Russo, Franco Roperto, Davide De Biase, Pellegrino Cerino, Chiara Urraro, John S. Munday and Sante Roperto

Pathogens 2020, 9(4), 262; https://doi.org/10.3390/pathogens9040262 - 04 Apr 2020

Cited by 6 | Viewed by 3192

Abstract

Multiple papillomatous nodules were observed scattered over the amniotic membrane in six water buffaloes that had recently aborted. Grossly, some of the nodules had multiple villous projections while others appeared as single prominent conical or cylindrical horns. Histology revealed folded hyperplastic and hyperkeratotic [...] Read more.

Multiple papillomatous nodules were observed scattered over the amniotic membrane in six water buffaloes that had recently aborted. Grossly, some of the nodules had multiple villous projections while others appeared as single prominent conical or cylindrical horns. Histology revealed folded hyperplastic and hyperkeratotic epithelium supported by a narrow fibro-vascular stalk. Using PCR, sequences of the bovine Deltapapillomavirus type 2 (BPV-2) E5 gene were amplified from the amniotic papillomas. Furthermore, expression of the E5 gene was detected using reverse transcription (RT)-PCR. Western blotting revealed BPV-2 E5 oncoprotein as well as L1 protein, suggesting both abortive and productive infection. Additionally, a functional complex composed of BPV-2 E5 oncoprotein and the phosphorylated PDGFβR was detected, which is consistent with the activation of PDGFβR by the interaction with BPV-2 E5 oncoprotein. These results demonstrate that BPV-2 can infect the amnion of water buffaloes and suggest that this infection may cause proliferation of the epithelial cells of the amnion. While the precise pathogenesis in uncertain, it is possible that BPV-2 infection of stratified squamous epithelial cells within squamous metaplasia foci and/or amniotic plaques could lead to papilloma formation. Papillomavirus-associated amniotic papillomas have not previously been reported in any species, including humans. Full article

(This article belongs to the Special Issue Bovine Papillomavirus Infection)

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11 pages, 1438 KiB

Open AccessEditor’s ChoiceArticle

Evaluation of Hypoxia-Inducible Factor-1 Alpha (HIF-1α) in Equine Sarcoid: An Immunohistochemical and Biochemical Study

by Manuela Martano, Gennaro Altamura, Karen Power, Brunella Restucci, Francesca Carella, Giuseppe Borzacchiello and Paola Maiolino

Pathogens 2020, 9(1), 58; https://doi.org/10.3390/pathogens9010058 - 14 Jan 2020

Cited by 5 | Viewed by 3060

Abstract

Background: equine sarcoids are the most frequent skin tumors in equidae worldwide. It is well known that delta bovine papillomaviruses are their causative agents. We have recently shown the presence in equine sarcoids of abnormal vessel structures, which could cause a hypoxic condition. [...] Read more.

Background: equine sarcoids are the most frequent skin tumors in equidae worldwide. It is well known that delta bovine papillomaviruses are their causative agents. We have recently shown the presence in equine sarcoids of abnormal vessel structures, which could cause a hypoxic condition. The aim of this study was to analyze the expression of hypoxia-inducible factor-1 alpha (HIF-1α) in a subset of BPV positive equine sarcoids and explore the relationship with vascular endothelial growth factor (VEGF) expression. Results: 80% of equine sarcoids showed strong cytoplasmic staining in >60% of neoplastic fibroblasts, while 20% of samples showed a moderate cytoplasmic staining in 40–60% of neoplastic fibroblasts for HIF-1α. Results of Western blotting (WB) were consistent with immunohistochemistry (IHC). Moreover, a positive correlation between HIF-1α and VEGF expression (r = 0.60, p < 0.01) was observed. Conclusion: we have shown that HIF-1α was strongly expressed in equine sarcoid. The upregulation of HIF-1α has been described in numerous tumors and can be modulated by many proteins encoded by transforming viruses. Thus, it is also possible that BPV could have a relevant role in HIF-1α pathway regulation, contributing to the development of equine sarcoids by promoting HIF-1α/VEGF mediated tumor angiogenesis. Full article

(This article belongs to the Special Issue Bovine Papillomavirus Infection)

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12 pages, 239 KiB

Open AccessReview

Anogenital-Associated Papillomaviruses in Animals: Focusing on Bos taurus Papillomaviruses

by Nanako Yamashita-Kawanishi and Takeshi Haga

Pathogens 2020, 9(12), 993; https://doi.org/10.3390/pathogens9120993 - 27 Nov 2020

Cited by 2 | Viewed by 1922

Abstract

In contrast to the diverse studies on human papillomaviruses (HPVs), information on animal PVs associated with anogenital lesions is limited. In the animal kingdom, papillomas occur more commonly in cattle than in any other animals, and diverse types of Bos taurus papillomaviruses (BPVs) [...] Read more.

In contrast to the diverse studies on human papillomaviruses (HPVs), information on animal PVs associated with anogenital lesions is limited. In the animal kingdom, papillomas occur more commonly in cattle than in any other animals, and diverse types of Bos taurus papillomaviruses (BPVs) exist, including the very recently discovered BPV type 29 (BPV29). From this perspective, we will review previous studies describing PV types associated with anogenitals in animals, with a focus on BPVs. To date, two classical BPV types, classified into Deltapapillomavirus (BPV1 and BPV2) and Dyokappapapillomavirus (BPV22), and two novel Xipapillomaviruses (BPV28 and BPV29) have been identified from anogenital lesions and tissues of the domestic cow. Due to the limited reports describing anogenital-associated PVs in animals, the relationships between their phylogenetic and pathogenetic properties are still undiscovered. Animal studies are valuable not only for the veterinary field but also for human medicine, as animal diseases have been shown to mimic human diseases. Studies of anogenital-associated PVs in animals have a positive impact on various research fields. Full article

(This article belongs to the Special Issue Bovine Papillomavirus Infection)

Other

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5 pages, 1495 KiB

Open AccessCase Report

Bovine Papillomatosis Hiding a Zoonotic Infection: Epitheliotropic Viruses in Bovine Skin Lesions

by Laura Gallina, Federica Savini, Sabrina Canziani, Matteo Frasnelli, Antonio Lavazza, Alessandra Scagliarini and Davide Lelli

Pathogens 2020, 9(7), 583; https://doi.org/10.3390/pathogens9070583 - 17 Jul 2020

Cited by 4 | Viewed by 3662

Abstract

We describe two cases of skin co-infections with epitheliotropic viruses, detected in two cattle during lumpy skin disease (LSD) surveillance in northern Italy. A diagnostic protocol including different molecular methods as well as negative staining electron microscopy was applied to detect the most [...] Read more.

We describe two cases of skin co-infections with epitheliotropic viruses, detected in two cattle during lumpy skin disease (LSD) surveillance in northern Italy. A diagnostic protocol including different molecular methods as well as negative staining electron microscopy was applied to detect the most common viral agents belonging to the family Papillomaviridae, Poxviridae and Herpesviridae which cause skin diseases in cattle. Two specimens were collected from cases clinically diagnosed as papillomatosis and pseudo-LSD. Both skin lesions were shown to harbor more than one viral species. This case report shows, for the first time, co-infection of zoonotic parapoxvirus with bovine papillomavirus and herpesvirus in skin lesions of cattle. In particular, the simultaneous presence of virions morphologically referable to parapoxvirus and papillomavirus confirms that the replication of both viruses in the same lesion can happen and the so-called papillomatosis can bear zoonotic viruses. Full article

(This article belongs to the Special Issue Bovine Papillomavirus Infection)

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