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The Journal of General Virology Dec 2014Papillomaviruses are a family of slowly evolving DNA viruses and their evolution is commonly linked to that of their host species. However, whilst bovine...
Analysis of the long control region of bovine papillomavirus type 1 associated with sarcoids in equine hosts indicates multiple cross-species transmission events and phylogeographical structure.
Papillomaviruses are a family of slowly evolving DNA viruses and their evolution is commonly linked to that of their host species. However, whilst bovine papillomavirus-1 (BPV-1) primarily causes warts in its natural host, the cow, it can also cause locally aggressive and invasive skin tumours in equids, known as sarcoids, and thus provides a rare contemporary example of cross-species transmission of a papillomavirus. Here, we describe the first phylogenetic analysis of BPV-1 in equine sarcoids to our knowledge, allowing us to explore the evolutionary history of BPV-1 and investigate its cross-species association with equids. A phylogenetic analysis of the BPV-1 transcriptional promoter region (the long control region or LCR) was conducted on 15 bovine and 116 equine samples from four continents. Incorporating previous estimates for evolutionary rates in papillomavirus implied that the genetic diversity in the LCR variants was ancient and predated domestication of both equids and cattle. The phylogeny demonstrated geographical segregation into an ancestral group (African, South American and Australian samples), and a more recently derived, largely European clade. Whilst our data are consistent with BPV-1 originating in cattle, we found evidence of multiple, probably relatively recent, cross-species transmission events into horses. We also demonstrated the high prevalence of one particular sequence variant (variant 20), and suggest this may indicate that this variant shows a fitness advantage in equids. Although strong host specificity remains the norm in papillomaviruses, our results demonstrate that exceptions to this rule exist and can become epidemiologically relevant.
Topics: Animals; Base Sequence; Bovine papillomavirus 1; Cattle; DNA, Viral; Female; Gene Expression Regulation, Viral; Genetic Variation; Horse Diseases; Horses; Locus Control Region; Male; Molecular Sequence Data; Papillomavirus Infections; Phylogeny; Phylogeography; Skin Neoplasms; Species Specificity; Tumor Virus Infections; Viral Proteins
PubMed: 25185436
DOI: 10.1099/vir.0.066589-0 -
Nucleic Acids Research May 1983A swedish isolate of bovine papillomavirus type 1 (BPV1) was cloned and a 4807 base pairs long sequence was determined, covering the entire late region of the BPV1... (Comparative Study)
Comparative Study
A swedish isolate of bovine papillomavirus type 1 (BPV1) was cloned and a 4807 base pairs long sequence was determined, covering the entire late region of the BPV1 genome and strategic parts of the early region. The sequence reveals two large uninterrupted reading frames, designated L1 and L2, which encode tentative polypeptides with molecular weights of 55.5 and 50.0 K. The promoter region for early transcription and the common 3'-end of early transcripts were identified in the sequence by performing S1 nuclease analysis of RNA isolated from a BPV1 transformed cell line. A detailed comparison between the established sequence and sequences from human papillomavirus type 1a (HPV1a) (1) and another BPV1 isolate (2) was also carried out. Only five differences were found when the sequences of the two BPV1 isolates were compared, two of which are located in reading frame L2. The results revealed furthermore that the genomes of BPV1 and HPV1a appear to be organized in a very similar fashion and the homology between reading frames L1 in BPV1 and HPV1 were particularly striking. A comparison of the established BPV1 sequence with sequences from SV40 and polyomavirus revealed no significant homology.
Topics: Animals; Base Sequence; Biological Evolution; Bovine papillomavirus 1; Cattle; DNA, Viral; Gene Expression Regulation; Humans; Papillomaviridae; RNA, Viral; Transcription, Genetic
PubMed: 6304656
DOI: 10.1093/nar/11.9.2639 -
Journal of Virology Mar 1998The bovine papillomavirus type 1 E2 transactivator protein is required for viral transcriptional regulation and DNA replication and may be important for long-term...
The bovine papillomavirus type 1 E2 transactivator protein is required for viral transcriptional regulation and DNA replication and may be important for long-term episomal maintenance of viral genomes within replicating cells (M. Piirsoo, E. Ustav, T. Mandel, A. Stenlund, and M. Ustav, EMBO J. 15:1-11, 1996). We have evidence that, in contrast to most other transcriptional transactivators, the E2 transactivator protein is associated with mitotic chromosomes in dividing cells. The shorter E2-TR and E8/E2 repressor proteins do not bind to mitotic chromatin, and the N-terminal transactivation domain of the E2 protein is necessary for the association. However, the DNA binding function of E2 is not required. We have found that bovine papillomavirus type 1 genomes are also associated with mitotic chromosomes, and we propose a model in which E2-bound viral genomes are transiently associated with cellular chromosomes during mitosis to ensure that viral genomes are segregated to daughter cells in approximately equal numbers.
Topics: Animals; Antigens, Polyomavirus Transforming; Bovine papillomavirus 1; CHO Cells; COS Cells; Cattle; Cell Line; Chlorocebus aethiops; Chromatin; Cricetinae; DNA, Viral; DNA-Binding Proteins; Genome, Viral; Mitosis; Sequence Deletion; Trans-Activators; Tumor Cells, Cultured; Viral Proteins
PubMed: 9499063
DOI: 10.1128/JVI.72.3.2079-2088.1998 -
Intervirology 2017This study aims to provide a molecular and epidemiological characterization of bovine papillomavirus (BPV) infections in Iraq.
OBJECTIVE
This study aims to provide a molecular and epidemiological characterization of bovine papillomavirus (BPV) infections in Iraq.
METHODS
The present study focuses on identifying BPV based on clinical and epidemiological manifestations, histopathological examinations, and polymerase chain reactions (PCR). Samples were collected from 163 animals suffering from cutaneous bovine papillomatosis, including 129 females (79.14%) with an age range of 16-40 months and 34 males (20.85%) with an age range of 17-29 months.
RESULTS
The incidence rate was significantly higher in females than in males. The most commonly affected sites were the teats and neck, though warts were found in other areas of the body. Histological sections were diagnosed as fibropapilloma. PCR results showed that 80.13% of the extracted papilloma DNA samples corresponded to the BPV-1 genotype. Furthermore, 7.94% of the samples showed a mixed infection of BPV-1 and BPV-13. While, 40.63% of the extracted DNA blood samples showed 2 DNA fragments corresponding to both genotypes BPV-1 and BPV-2.
CONCLUSIONS
This study confirmed the presence of BPV-1, BPV-2, and BPV-13, which belong to the Deltapapillomavirus genera, for the first time in the DNA of Iraqi cattle. Understanding BPV diversity and epidemiology is of critical importance for starting prevention strategies.
Topics: Animals; Cattle; Cattle Diseases; Female; Genotype; Histocytochemistry; Iraq; Male; Molecular Epidemiology; Papilloma; Papillomaviridae; Papillomavirus Infections; Polymerase Chain Reaction
PubMed: 29428951
DOI: 10.1159/000486594 -
Journal of Virology Nov 1984Bovine papillomavirus type 1 (BPV-1) or cloned BPV-1 DNA can transform susceptible rodent cells, and the viral DNA remains as a stable extrachromosomal plasmid in the...
Bovine papillomavirus type 1 (BPV-1) or cloned BPV-1 DNA can transform susceptible rodent cells, and the viral DNA remains as a stable extrachromosomal plasmid in the transformed cells. The transforming region of the BPV-1 genome has previously been localized to a specific fragment comprising 69% of the genome, which also contains the elements sufficient for extrachromosomal plasmid maintenance. To define more precisely the viral DNA sequences which are involved in cellular transformation, we have tested the ability of defined deletion mutants of BPV-1 DNA to morphologically transform mouse C127 cells. Cells containing the mutated DNAs have been examined for anchorage independence and tumorigenicity in nude mice. Several distinct regions of the BPV-1 genome were found to influence expression of the viral transformation functions. A transcriptional regulatory region located in the noncoding region 5' to the early open reading frames is essential for transcriptional activity and transformation. A transcriptional enhancer element, located 3' to the polyadenylation site for the viral RNAs expressed in transformed cells, has previously been shown to be essential for transformation (Lusky et al., Mol. Cell. Biol., 3:1108-1122, 1983). Deletion mutants affecting the E2 open reading frame, particularly the NH2 half, are significantly impaired in their ability to transform, suggesting that the E2 gene product is an important transforming protein of BPV-1. Mutants lacking the E6 and E7 open reading frames are still able to induce transformation but at a lowered efficiency, and the transformants have altered characteristics. Mutations localized within the E1 open reading frame do not significantly affect the transforming functions but result in the integration of the viral genome in the transformed cells, implicating the E1 gene product in stable plasmid replication and maintenance.
Topics: Animals; Bovine papillomavirus 1; Cell Adhesion; Cell Line; Cell Transformation, Viral; Chromosome Deletion; DNA Restriction Enzymes; DNA, Viral; Genes, Viral; Genetic Complementation Test; Mice; Mutation; Papillomaviridae
PubMed: 6092667
DOI: 10.1128/JVI.52.2.377-388.1984 -
Genetics and Molecular Research : GMR 2008Bovine papillomavirus (BPV) DNA sequences were detected in different tissues, in addition to epithelium. Cytogenetic abnormalities were observed in blood lymphocytes....
Bovine papillomavirus (BPV) DNA sequences were detected in different tissues, in addition to epithelium. Cytogenetic abnormalities were observed in blood lymphocytes. The presence of more than one virus in a single tissue is a difficult aspect to evaluate, especially when the DNA sequences are detected in tissues that are not specifically targeted by the virus. BPV and bovine leukemia virus (BLV) are clastogenic, causing chromosome aberrations in peripheral blood lymphocytes. In the present study, we investigated the simultaneous presence of DNA sequences of both viruses and the possibility of vertical transmission and compared the types of chromosome aberrations related to viral action. BPV 1, 2, and 4 DNA sequences were found in three females of the herd and in their offspring. BLV DNA sequences were not detected in their progeny. A newborn calf that was negative for BLV infection showed specific chromosome rearrangements possibly related to the effect of infection with BPV.
Topics: Animals; Animals, Newborn; Bovine papillomavirus 1; Cattle; Chromosome Aberrations; Chromosome Banding; Cytogenetic Analysis; Enzootic Bovine Leukosis; Female; In Situ Hybridization; Karyotyping; Leukemia Virus, Bovine; Papillomavirus Infections; Polymerase Chain Reaction
PubMed: 18561382
DOI: 10.4238/vol7-2gmr436 -
Journal of Virology Feb 1990The methionine codon at bovine papillomavirus type 1 nucleotide 3091 was mutated to determine whether it may serve as an initiation codon for an E2 transcriptional...
The methionine codon at bovine papillomavirus type 1 nucleotide 3091 was mutated to determine whether it may serve as an initiation codon for an E2 transcriptional repressor protein and to determine the role of the repressor in the biological activities of the virus. A series of transient expression experiments with CV1 cells documented that the mutation reduced expression of repressor activity from the viral genome and resulted in increased expression of the E5 transforming gene. Viral genomes containing the mutation displayed enhanced transforming activity in several assays in mouse C127 cells, including focus formation, colony formation in agarose, and tumorigenicity. In transformed cells, the mutant viral DNA was maintained as a plasmid with approximately 500 genomes per cell, whereas the wild-type copy number was approximately 75. These results indicate that the wild-type bovine papillomavirus type 1 genome encodes an E2 repressor protein that moderates the viral transforming activity and allows maintenance of the viral DNA at a relatively low copy number.
Topics: Animals; Bovine papillomavirus 1; Cell Line; Cell Transformation, Neoplastic; DNA, Viral; Genes, Regulator; Genes, Viral; Mutation; Oligonucleotide Probes; Papillomaviridae; Phenotype; Transcriptional Activation
PubMed: 2153255
DOI: 10.1128/JVI.64.2.944-949.1990 -
Journal of Virology Apr 1992Bovine papillomavirus type 1 (BPV-1) has served as the prototype papillomavirus for the study of viral transcription, DNA replication, and latency. However, no cis...
Bovine papillomavirus type 1 (BPV-1) has served as the prototype papillomavirus for the study of viral transcription, DNA replication, and latency. However, no cis essential transcription control regions which are necessary for both transformation and replication of BPV-1 or any other papillomavirus have yet been defined. We have found that BPV-1 mutants with deletions in the long control region were defective for transformation and replication, with the essential region in the 5' long control region corresponding to the previously defined BPV-1 constitutive enhancer (S. B. Vande Pol and P. M. Howley, J. Virol. 64:5420-5429, 1990). BPV-1 mutants deleted of the constitutive enhancer could be complemented in trans by the full-length virally encoded E2 transactivator and replication factor (E2TA) and in cis by the simian virus 40 enhancer. The constitutive enhancer induced the production of E2TA by activating all the major viral early promoters upstream of the E2 open reading frame. Complementation experiments using a temperature-sensitive E2TA mutant indicated that the constitutive enhancer was necessary for the maintenance of viral DNA replication within latently infected cells and implied that viral transcription under the regulation of the constitutive enhancer may be controlled during the cell cycle. The constitutive enhancer is a master regulatory control region for establishing and maintaining BPV-1 latency, and its characteristics reveal some analogies with cell type-specific enhancer elements recognized in the human papillomaviruses.
Topics: Animals; Blotting, Southern; Bovine papillomavirus 1; Cattle; Cell Line; Cell Transformation, Viral; DNA Replication; DNA, Viral; Enhancer Elements, Genetic; Genetic Complementation Test; Mice; Plasmids; Regulatory Sequences, Nucleic Acid; Restriction Mapping; Transcription, Genetic; Virus Activation
PubMed: 1312634
DOI: 10.1128/JVI.66.4.2346-2358.1992 -
Virology Journal Feb 2012Human papillomavirus (HPV) vaccines based on major capsid protein L1 are licensed in over 100 countries to prevent HPV infections. The yeast-derived recombinant...
BACKGROUND
Human papillomavirus (HPV) vaccines based on major capsid protein L1 are licensed in over 100 countries to prevent HPV infections. The yeast-derived recombinant quadrivalent HPV L1 vaccine, GARDASIL(R), has played an important role in reducing cancer and genital warts since its introduction in 2006. The L1 proteins self-assemble into virus-like particles (VLPs).
RESULTS
VLPs were subjected to post-purification disassembly and reassembly (D/R) treatment during bioprocessing to improve VLP immunoreactivity and stability. The post-D/R HPV16 VLPs and their complex with H16.V5 neutralizing antibody Fab fragments were visualized by cryo electron microscopy, showing VLPs densely decorated with antibody. Along with structural improvements, post-D/R VLPs showed markedly higher antigenicity to conformational and neutralizing monoclonal antibodies (mAbs) H16.V5, H16.E70 and H263.A2, whereas binding to mAbs recognizing linear epitopes (H16.J4, H16.O7, and H16.H5) was greatly reduced. Strikingly, post-D/R VLPs showed no detectable binding to H16.H5, indicating that the H16.H5 epitope is not accessible in fully assembled VLPs. An atomic homology model of the entire HPV16 VLP was generated based on previously determined high-resolution structures of bovine papillomavirus and HPV16 L1 pentameric capsomeres.
CONCLUSIONS
D/R treatment of HPV16 L1 VLPs produces more homogeneous VLPs with more virion-like antibody reactivity. These effects can be attributed to a combination of more complete and regular assembly of the VLPs, better folding of L1, reduced non-specific disulfide-mediated aggregation and increased stability of the VLPs. Markedly different antigenicity of HPV16 VLPs was observed upon D/R treatment with a panel of monoclonal antibodies targeting neutralization sensitive epitopes. Multiple epitope-specific assays with a panel of mAbs with different properties and epitopes are required to gain a better understanding of the immunochemical properties of VLPs and to correlate the observed changes at the molecular level. Mapping of known antibody epitopes to the homology model explains the changes in antibody reactivity upon D/R. In particular, the H16.H5 epitope is partially occluded by intercapsomeric interactions involving the L1 C-terminal arm. The homology model allows a more precise mapping of antibody epitopes. This work provides a better understanding of VLPs in current vaccines and could guide the design of improved vaccines or therapeutics.
Topics: Antibodies, Viral; Antibody Affinity; Capsid Proteins; Epitope Mapping; Epitopes; Human papillomavirus 16; Humans; Models, Molecular; Oncogene Proteins, Viral; Papillomaviridae; Papillomavirus Vaccines; Protein Binding; Protein Conformation; Virion; Virus Assembly
PubMed: 22356831
DOI: 10.1186/1743-422X-9-52 -
Journal of Virology Jul 1991
Review
Topics: Animals; Bovine papillomavirus 1; DNA Replication; Genes, Viral; Humans; Papillomaviridae; Viral Proteins; Viral Structural Proteins; Virus Replication
PubMed: 1645776
DOI: 10.1128/JVI.65.7.3417-3420.1991