Publications

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role of l2 cysteines in papillomavirus infection and neutralization.vaccination of mice with minor capsid protein l2 or passive transfer with the l2-specific neutralizing monoclonal antibody rg-1 protects against human papillomavirus type 16 (hpv16) challenge. here we explored the nature of the rg-1 epitope and its contribution to viral infectivity. rg-1 bound equivalently hpv16 l2 residues 17-36 with or without an intact c22-c28 disulphide bridge. hpv16 l2 mutations k20a, c22a, c22s, c28a, c28s, or p29a prevented rg-1 binding, whereas y19a, k23a or q24a had no ...200919860897
enhancing efficacy and mucosa-tropic distribution of an oral hiv-psv dna vaccine in animal models.a strategy combined the oral delivery route and bovine papillomavirus (bpv) pseudovirus (psv)-based human immunodeficiency virus (hiv) dna vaccine, which has been proven to enhance the mucosal immunization compared with the systemic immunization and in general does not induce effective mucosal immune responses. in this study, the immune responses against the bpv expressing hiv gp41 epitopes (eldkwa, nwfdit) after oral administration in cynomolgus monkeys (macaca fascicularis) were assessed, and ...200919863197
simultaneous presence of bovine papillomavirus in blood and in short-term lymphocyte cultures from dairy cattle in pernambuco, brazil.bovine papillomaviruses (bpv) are the causal agents of benign and malignant lesions; they can cause dramatic economic losses in cattle. although 10 virus types have been described, three types are most common in tumors, namely bpv-1, -2 and -4. previous studies have reported bpv in blood cells and the possibility of blood acting as a latent virus site and/or transmission agent of virus dissemination. we studied a holstein dairy herd in pernambuco, brazil, in which several animals showed severe c ...200920082260
bovine papillomavirus type 9 induces epithelial papillomas on the teat skin of heifers.experiments were carried out to investigate whether papillomas could be induced on the teat skin of heifers by intradermal injection with bovine papillomavirus type 9 (bpv-9). three heifers (#1 and 2, two 0.5-year-old holsteins; #3, a 1.5-year-old japanese black) were injected with bpv-9 and one heifer (#4, a 0.5-year-old holstein) was mock-infected. viral dna load in the inocula was quantified by real-time polymerase chain reaction assay and adjusted to 1.56x10(12) copies per injection. papillo ...200919095383
tax1bp1 interacts with papillomavirus e2 and regulates e2-dependent transcription and stability.the papillomavirus e2 proteins regulate viral replication, gene transcription, and genome maintenance by interacting with other viral and host proteins. from a yeast two-hybrid screen, we identified the cellular protein tax1bp1 as a novel binding partner of human papillomavirus type 18 (hpv18) e2. tax1bp1 also interacts with the hpv16 and bovine papillomavirus type 1 (bpv1) e2 proteins, with the c-terminal region of tax1bp1 interacting with the n-terminal transactivation domain of bpv1 e2. tax1b ...200919109394
papillomavirus e2 proteins and the host brd4 protein associate with transcriptionally active cellular chromatin.the interaction of papillomavirus e2 proteins with cellular brd4 protein is important for transcriptional regulation of viral genes and partitioning of viral genomes. bovine papillomavirus type 1 (bpv-1) e2 binds cellular chromatin in complex with brd4 in both mitotic and interphase cells. to identify specific sites of e2 interaction on cellular chromatin, a genome-wide chromatin immunoprecipitation-on-chip analysis was carried out using human promoter sequences. both e2 and brd4 were found boun ...200919129460
pleomorphic corneal sarcoma resembling malignant peripheral nerve sheath tumor in a horse.a 14-year-old haflinger gelding presented with a protruding mass involving the cornea of the right eye. the mass was resected and submitted for histopathologic and immunohistochemical examination. the preliminary diagnosis was corneal sarcoma, most likely fibrosarcoma. the immunohistochemical results confirmed the mesenchymal origin of the neoplastic cells, which were most consistent with a malignant peripheral nerve sheath tumor. corneal mesenchymal neoplasms are extremely uncommon tumors in hu ...200919176499
plasmids with e2 epitope tags: tagging modules for n- and c-terminal pcr-based gene targeting in both budding and fission yeast, and inducible expression vectors for fission yeast.a single-step pcr-based epitope tagging enables fast and efficient gene targeting with various epitope tags. this report presents a series of plasmids for the e2 epitope tagging of proteins in saccharomyces cerevisiae and schizosaccharomyces pombe. e2tags are 10-amino acids (epitope e2a: sstssdfrdr)- and 12 amino acids (epitope e2b: gvsstssdfrdr)-long peptides derived from the e2 protein of bovine papillomavirus type 1. the modules for c-terminal tagging with e2a and e2b epitopes were constructe ...200919180640
bovine papillomavirus type 1 e2 protein heterodimer is functional in papillomavirus dna replication in vivo.papillomaviruses are small dna viruses that induce epithelial lesions in their host. the viral life cycle is regulated by the family of proteins encoded by the e2 open reading frame. in addition to the full-length e2 protein, the bpv-1 genome encodes two truncated e2 proteins, e2c and e8/e2, which maintain the dna-binding-dimerization domains, but lack the activation domain. heterodimers formed between the full-length e2 and truncated e2 proteins serve as activators of e2-dependent transcription ...200919232665
regulation of bovine papillomavirus type 1 gene expression by rna processing.bovine papillomavirus type 1 (bpv-1) has served as a prototype for studying the molecular biology and pathogenesis of papillomaviruses. the expression of bpv-1 early and late genes is highly regulated at both transcription and post-transcriptional levels and strictly tied to the differentiation of keratinocytes. bpv-1 infects keratinocytes in the basal layer of the skin and replicates in the nucleus of infected cells in a differentiation-dependent manner. although viral early genes begin to be e ...200919273129
bovine papillomavirus type 1 dna and e5 oncoprotein expression in water buffalo fibropapillomas.papillomas and fibropapillomas may occur in the skin and in different organs in animals. ten different genotypes of bovine papillomavirus (bpv) have been identified. bpv-1 through bpv-10 are all strictly species-specific, but bpv-1/2 may also infect other species such as equids, inducing fibroblastic tumors. bpv-1 and bpv-2 are associated with fibropapillomas in cattle; these tumors are formed by excessive proliferation of virus-infected dermal fibroblasts and epidermal keratinocytes. nine water ...200919276046
activated platelet-derived growth factor beta receptor expression, pi3k-akt pathway molecular analysis, and transforming signals in equine sarcoids.the equine sarcoid is the most common dermatologic neoplasm reported in horses. bovine papillomavirus (bpv) types 1 and 2 are associated with sarcoids, in which the expression of the major transforming oncoprotein (e5) is often recorded. the transformation activity of the virus is due to the binding of the e5 to the platelet-derived growth factor beta receptor (pdgfbeta-r). in the present study, we show by western blot in 4 sarcoid samples and 3 normal equine skin samples that the pdgfbeta-r is ...200919276057
bovine papillomavirus dna in milk, blood, urine, semen, and spermatozoa of bovine papillomavirus-infected animals.papillomavirus infection in bovines is associated with cutaneous papillomatosis on the hide, udders and other epithelial tissues, as well as in oral respiratory, alimentary and urinary tract mucosa. bovine papillomavirus (bpv) is also considered the etiological agent of esophageal tumors and the malignant bladder tumors that characterize the clinical condition associated with chronic enzootic hematuria. after infective viral dna was found in cattle blood and bpv1, 2 and 4 dna in cattle reproduct ...200919291880
the bovine papillomavirus e5 protein and the pdgf beta receptor: it takes two to tango.the extremely hydrophobic, 44-amino acid bovine papillomavirus (bpv) e5 protein is the smallest known oncoprotein, which orchestrates cell transformation by causing ligand-independent activation of a cellular receptor tyrosine kinase, the platelet-derived growth factor beta receptor (pdgfbetar). the e5 protein forms a dimer in transformed cells and is essentially an isolated membrane-spanning segment that binds directly to the transmembrane domain of the pdgfbetar, inducing receptor dimerization ...200918990418
the human papillomavirus type 8 e2 tethering protein targets the ribosomal dna loci of host mitotic chromosomes.for many papillomaviruses, the viral protein e2 tethers the viral genome to the host mitotic chromosomes to ensure persistent, long-term maintenance of the genome during cell division. our previous studies of e2 proteins from different genera of papillomaviruses have shown that they bind to different regions of the host chromosomes during mitosis. for example, bovine papillomavirus type 1 (bpv-1) e2 binds to all chromosomes as small speckles in complex with the cellular protein brd4. in contrast ...200919004936
the detection of bovine papillomavirus type 1 dna in flies.bpvs are double stranded dna viruses that can infect several species other than the natural host, cattle, including equids. in equids, bpv-1, and, less commonly bpv-2, infection gives rise to fibroblastic tumours of the skin. whilst a causal relationship between bpv-1/2 and equine sarcoids is now well established, how the disease is transmitted is not known. in this study we show bpv-1 dna can be detected in flies trapped in the proximity of sarcoid-affected animals. sequence analysis of the bpv ...200919409942
co-expression of bovine papillomavirus e5 and e7 oncoproteins in naturally occurring carcinomas of the urinary bladder in cattle.the aetiopathogenesis of urinary bladder tumours in cattle involves prolonged ingestion of bracken fern and infection by bovine papillomavirus (bpv). the aim of the present study was to determine whether there was co-expression of bpv oncoproteins e5 and e7 in such urothelial carcinomas. fifteen samples were shown by immunohistochemistry to express e7 with labelling of both the cytoplasm and nucleus, in addition to labelling of the urothelial cell membrane. three of these samples were subsequent ...200919410260
cellular factors are required to activate bovine papillomavirus-1 early gene transcription and to establish viral plasmid persistence but are not required for cellular transformation.transcription from the major upstream early gene promoter, p89, of bovine papillomavirus (bpv)-1 is detectable in transfected cells lacking viral gene products yet also responds to viral e2 proteins. in contrast to human papillomaviruses (hpvs), the bpv upstream regulatory region (urr) functions as a transcriptional enhancer in epithelial cells and fibroblasts of bovine, murine or human origin. mutations of sp1 and/or two novel transcriptional enhancer factor (tef)-1 sites within the 5' urr of t ...200919410271
detection of bovine papillomavirus dna in sarcoid-affected and healthy free-roaming zebra (equus zebra) populations in south africa.the endangered cape mountain zebra (equus zebra zebra) is protected in small numbers in a few isolated populations in south african game parks. since 1995, sarcoid lesions appeared in zebras in two of the parks. this study was undertaken to investigate if bovine papillomavirus (bpv) is associated with sarcoids in these zebras. a conventional pcr, targeting the e5 orf of bpv, and subsequent rflp analysis were initially used to demonstrate the presence of bpv-1 and -2 dnas in zebra sarcoid tumours ...200919428583
human papillomavirus research: do we still need animal models? 200919441096
guanine exchange factor vav2: a novel potential target for the development of drugs effective in the prevention of papillomavirus infection and disease.the bovine papillomavirus capsid protein l2 has no homology to known cellular proteins. we identified the interaction of bovine papillomavirus type 1 l2 with the guanine exchange factor vav2. we determined that the interaction of l2 with vav2 was mediated by the n-terminus of l2 and independent of the n-terminus of vav2. l2 expression resulted in a change in the intracellular expression of vav2 from diffuse to punctate cytoplasmic pattern. our experiments in human epithelial cells showed that l2 ...200919451809
human papillomavirus type 16 infection of human keratinocytes requires clathrin and caveolin-1 and is brefeldin a sensitive.human papillomavirus type 16 (hpv16) has been identified as being the most common etiological agent leading to cervical cancer. despite having a clear understanding of the role of hpv16 in oncogenesis, details of how hpv16 traffics during infection are poorly understood. hpv16 has been determined to enter via clathrin-mediated endocytosis, but the subsequent steps of hpv16 infection remain unclear. there is emerging evidence that several viruses take advantage of cross talk between routes of end ...200919494002
ifn-gamma promotes generation of il-10 secreting cd4+ t cells that suppress generation of cd8 responses in an antigen-experienced host.ags characterizing tumors or chronic viral infection are generally presented to the host immune system before specific immunotherapy is initiated, and consequent generation of regulatory cd4(+) t cells can inhibit induction of desired effector cd8 t cell responses. il-10 produced in response to ongoing ag exposure inhibits generation of cd8 t cells in an ag-experienced host. we now show that this il-10 is produced by ag experienced cd4(+) glucocorticoid-induced tumor necrosis factor receptor(+) ...200919535638
brd4 regulation of papillomavirus protein e2 stability.the papillomavirus (pv) e2 protein is an important regulator of the viral life cycle. it has diverse roles in viral transcription, dna replication, and genome maintenance. our laboratory has previously identified the cellular bromodomain protein brd4 as a key interacting partner of e2. brd4 mediates the transcriptional activation function of e2 and plays an important role in viral genome maintenance in dividing cells. e2 interacts with the c-terminal domain (ctd) of brd4, and the ctd functions i ...200919553317
dna structure modulates the oligomerization properties of the aav initiator protein rep68.rep68 is a multifunctional protein of the adeno-associated virus (aav), a parvovirus that is mostly known for its promise as a gene therapy vector. in addition to its role as initiator in viral dna replication, rep68 is essential for site-specific integration of the aav genome into human chromosome 19. rep68 is a member of the superfamily 3 (sf3) helicases, along with the well-studied initiator proteins simian virus 40 large t antigen (sv40-ltag) and bovine papillomavirus (bpv) e1. structurally, ...200919593381
artificial transmembrane oncoproteins smaller than the bovine papillomavirus e5 protein redefine sequence requirements for activation of the platelet-derived growth factor beta receptor.the bovine papillomavirus e5 protein (bpv e5) is a 44-amino-acid homodimeric transmembrane protein that binds directly to the transmembrane domain of the platelet-derived growth factor (pdgf) beta receptor and induces ligand-independent receptor activation. three specific features of bpv e5 are considered important for its ability to activate the pdgf beta receptor and transform mouse fibroblasts: a pair of c-terminal cysteines, a transmembrane glutamine, and a juxtamembrane aspartic acid. by us ...200919605488
small interfering rna targeting bovine papillomavirus type 1 e2 induces apoptosis in equine sarcoid transformed fibroblasts.equine sarcoids are skin tumours of horses caused by infection with bpv-1 or 2. maintenance and replication of the viral genome depend upon the viral proteins e1 and e2. we examined the effects of an e2 specific sirna on e2 and e1 viral gene expression, viral load and cell growth in bpv-1 transformed sarcoid-derived cells. transfection with e2-sirna caused a reduction in e2 and e1 mrna expression as well as viral load, growth inhibition and decreased anchorage-independent growth. sirna treated c ...200919615418
persistent immune responses induced by a human immunodeficiency virus dna vaccine delivered in association with electroporation in the skin of nonhuman primates.strategies to improve vaccine efficacy are still required, especially in the case of chronic infections, including human immunodeficiency virus (hiv). dna vaccines have potential advantages over conventional vaccines; however, low immunological efficacy has been demonstrated in many experiments involving large animals and in clinical trials. to improve the immunogenicity of dna vaccines, we have designed a plasmid vector exploiting the binding capacity of the bovine papillomavirus e2 protein and ...200919627235
chimeric l1-l2 virus-like particles as potential broad-spectrum human papillomavirus vaccines.the amino (n) terminus of the human papillomavirus (hpv) minor capsid protein l2 can induce low-titer, cross-neutralizing antibodies. the aim of this study was to improve immunogenicity of l2 peptides by surface display on highly ordered, self-assembled virus-like particles (vlp) of major capsid protein l1, and to more completely characterize neutralization epitopes of l2. overlapping peptides comprising amino acids (aa) 2 to 22 (hereafter, chimera or peptide 2-22), 13 to 107, 18 to 31, 17 to 36 ...200919640991
bovine papillomavirus type 1 oncoprotein e5 inhibits equine mhc class i and interacts with equine mhc i heavy chain.bovine papillomavirus type 1 is one of the aetiological agents of equine sarcoids. the viral major oncoprotein e5 is expressed in virtually all sarcoids, sarcoid cell lines and in vitro-transformed equine fibroblasts. to ascertain whether e5 behaves in equine cells as it does in bovine cells, we introduced the e5 open reading frame into fetal equine fibroblasts (eqpalf). as observed in primary bovine fibroblasts (bopalf), e5 by itself could not immortalize eqpalf and an immortalizing gene, such ...200919675187
topography of bovine papillomavirus e2 protein on the viral genome during the cell cycle.the multifunctional papillomavirus e2 protein serves important roles in transcriptional activation and genome maintenance and cooperates with the viral e1 helicase for the initiation of viral dna replication. the bovine papillomavirus genome contains seventeen e2 binding sites, largely concentrated within the long control region, and a single e1 binding site at the origin of viral replication. using chromatin immunoprecipitation (chip) followed by restriction enzyme digestion and pcr, we show th ...200919716579
bovine papillomavirus type 1 (bpv1) and bpv2 are closely related serotypes.infection with bovine papillomavirus type 1 (bpv1) or bpv2 induces fibropapillomas in cows and skin sarcoids in horses. prophylactic vaccination targeting bpv1 and bpv2 may reduce the incidence of these economically important diseases. the l1 major capsid proteins of bpv1 and bpv2 were expressed in sf-9 insect cells and both self-assembled into virus-like particles (vlps). using conformation-dependent monoclonal antibodies (mab) both type-specific and shared epitopes were detected. antisera were ...200919729180
control of the papillomavirus early-to-late switch by differentially expressed srp20.the viral early-to-late switch of papillomavirus infection is tightly linked to keratinocyte differentiation and is mediated in part by alternative mrna splicing. here, we report that srp20, a cellular splicing factor, controls the early-to-late switch via interactions with a/c-rich rna elements. an a/c-rich se4 element regulates the selection of a bovine papillomavirus type 1 (bpv-1) late-specific splice site, and binding of srp20 to se4 suppresses this selection. expression of late bpv-1 l1 or ...200918945760
a review of bovine urothelial tumours and tumour-like lesions of the urinary bladder.four hundred bovine urothelial tumours and tumour-like lesions were classified in accordance with the 2004 world health organization (who) morphological classification for human urothelial tumours. the spectrum of neoplastic lesions of the urinary bladder of cattle is becoming wider and bovine urothelial tumours share striking morphological features with their human counterparts. a classification system based on the who scheme would also be appropriate for the classification of bovine bladder tu ...201019818448
sigma-2 receptor expression in bovine papillomavirus-associated urinary bladder tumours.the expression of sigma-2 receptors was investigated in nine urothelial tumours of the urinary bladder of cattle. each tumour was associated with the presence of dna of bovine papillomavirus type-2 (bpv-2) and expression of the e5 viral oncoprotein. five tumours were classified as low-grade carcinoma on the basis of morphological criteria and calculation of mean nuclear area (mna) and mean nuclear perimeter (mnp). four tumours were classified as high-grade carcinoma. sigma-2 receptors were overe ...201019631333
ferritin heavy chain (fhc) is up-regulated in papillomavirus-associated urothelial tumours of the urinary bladder in cattle.the up-regulation of ferritin heavy chain (fhc) is reported in six papillary and in four invasive urothelial tumours of the urinary bladder of cattle grazing on mountain pastures rich in bracken fern. all tumours contained sequence of bovine papillomavirus type-2 (bpv-2) as determined by polymerase chain reaction (pcr) analyses and validated by direct sequencing of the amplified products. the oncoprotein e5 was also detected in these tumours by immunoprecipitation and by immunofluorescence and l ...201019596355
bovine papillomavirus type 1 e2 and e7 proteins down-regulate toll like receptor 4 (tlr4) expression in equine fibroblasts.bpv-1 and less commonly bpv-2 are associated with the pathogenesis of equine skin tumours termed sarcoids. we recently documented the transcriptional changes that are induced by bpv-1 in equine fibroblasts using microarray analyses. tlr4 expression was found to be significantly down-regulated by bpv-1. in the present study, we show that tlr4 expression is significantly decreased following the exogenous expression of bpv-1 e2 and e7 in primary equine fibroblasts. the results were confirmed by the ...201020109504
detection of bpv-1 and -2 and quantification of bpv-1 by real-time pcr in cutaneous warts in cattle and buffaloes.bovine cutaneous warts (cws) were investigated in northern india. of 49 cases, 44 were recorded in cattle and 5 in buffaloes. these animals had mild to moderate grade infections. grossly, cases of cws appeared to be of exophytic type, however, different types of growth patterns were observed. a total of 26 biopsies (cattle 21 and buffaloes 5) from cws-affected animals studied histopathologically were diagnosed as exophytic and cauliflower-like fibropapilloma 13, exophytic and dome-shaped fibropa ...201020113447
genome-wide sirna screen identifies smcx, ep400, and brd4 as e2-dependent regulators of human papillomavirus oncogene expression.an essential step in the pathogenesis of human papillomavirus (hpv)-associated cancers is the dysregulated expression of the viral oncogenes. the papillomavirus e2 protein can silence the long control region (lcr) promoter that controls viral e6 and e7 oncogene expression. the mechanisms by which e2 represses oncogene expression and the cellular factors through which e2 mediates this silencing are largely unknown. we conducted an unbiased, genome-wide sirna screen and series of secondary screens ...201020133580
construction and genetic selection of small transmembrane proteins that activate the human erythropoietin receptor.this work describes a genetic approach to isolate small, artificial transmembrane (tm) proteins with biological activity. the bovine papillomavirus e5 protein is a dimeric, 44-amino acid tm protein that transforms cells by specifically binding and activating the platelet-derived growth factor beta receptor (pdgfbetar). we used the e5 protein as a scaffold to construct a retrovirus library expressing approximately 500,000 unique 44-amino acid proteins with randomized tm domains. we screened this ...201020142506
structure-based mutational analysis of the bovine papillomavirus e1 helicase domain identifies residues involved in the nonspecific dna binding activity required for double trimer formation.the papillomavirus e1 protein is a multifunctional initiator protein responsible for preparing the viral dna template for initiation of dna replication. the e1 protein encodes two dna binding activities that are required for initiation of dna replication. a well-characterized sequence-specific dna binding activity resides in the e1 dbd and is used to tether e1 to the papillomavirus ori. a non-sequence-specific dna binding activity is also required for formation of the e1 double trimer (dt) compl ...201020147403
common importin alpha specificity for papillomavirus e2 proteins.papillomaviruses infect keratinocytes and their reproduction is tied to differentiation of the skin. the e2 protein of papillomaviruses is a multifunctional early protein that binds specifically to the viral dna to regulate genome transcription, replication, and segregation. all of these are nuclear events that require specific transport of e2 into the host nucleus. nuclear localization signal (nls) sequences have been mapped for several e2 proteins, and these sequences resemble motifs that inte ...201020193720
subunit interactions in bovine papillomavirus.papillomaviruses, members of a group of dsdna viruses associated with epithelial growths and tumors, have compact capsids assembled from 72 pentamers of the protein l1. we have determined the structure of bovine papillomavirus by electron cryomicrosopy (cryoem), at approximately 3.6 a resolution. the density map, obtained from single-particle analysis of approximately 4,000 particle images, shows the trace of the l1 polypeptide chain and reveals how the n- and c-terminal "arms" of a subunit (ext ...201020308582
influenza virus activates inflammasomes via its intracellular m2 ion channel.influenza virus, a negative-stranded rna virus that causes severe illness in humans and animals, stimulates the inflammasome through the nod-like receptor nlrp3. however, the mechanism by which influenza virus activates the nlrp3 inflammasome is unknown. here we show that the influenza virus m2 protein, a proton-selective ion channel important in viral pathogenesis, stimulates the nlrp3 inflammasome pathway. m2 channel activity was required for the activation of inflammasomes by influenza and wa ...201020383149
calpain3 is expressed in a proteolitically active form in papillomavirus-associated urothelial tumors of the urinary bladder in cattle.calpain 3 (capn3), also named p94, is a skeletal muscle tissue-specific protein known to be responsible for limb-girdle muscular dystrophy type 2a (lgmd2a). recent experimental studies have hypothesized a pro-apoptotic role of capn3 in some melanoma cell lines. so far the link between calpain3 and tumors comes from in vitro studies. the objective of this study was to describe capn3 activation in naturally occurring urothelial tumors of the urinary bladder in cattle.201020421977
phosphatidylinositol-3-kinase-akt pathway, phospho-jun and phospho-jnk expression in spontaneously arising bovine urinary bladder tumours.the aetiopathogenesis of urinary bladder tumours in cattle involves prolonged ingestion of bracken fern and infection by bovine papillomavirus types 1 or 2 (bpv-1/2). e5, the major bpv-1/2 oncoprotein, binds to the activated platelet-derived growth factor beta receptor (ppdgf-betar), inducing cell transformation in vitro and spontaneously arising urinary bladder tumours. the aim of this study was to assess whether the 85 kda regulatory subunit (p85) of the phosphatidylinositol-3-kinase (pi3k)-ak ...201020427051
intralesional bovine papillomavirus dna loads reflect severity of equine sarcoid disease.sarcoids are nonmetastasising, yet locally aggressive skin tumours that constitute the most frequent neoplasm in equids. infection by bovine papillomaviruses types 1 and 2 (bpv-1, bpv-2) has been recognised as major causative factor in sarcoid pathogenesis, but a possible correlation of intralesional virus load with disease severity has not been established thus far.201020525051
equine sarcoid fibroblasts over-express matrix metalloproteinases and are invasive.papillomaviruses are dna viruses that cause tumours of the skin in humans and animals. the natural host of bovine papillomavirus is cattle, but also equids, resulting in tumours termed sarcoids. matrix metalloproteinase 1 (mmp-1) expression is up-regulated in sarcoid fibroblasts and tumours. we extended our observation to other mmps and determined whether mmps induced invasion of sarcoid fibroblasts. collagenase (mmp-1) and gelatinase (mmp-2, mmp-9) were over-expressed in sarcoid fibroblasts and ...201019896685
e6 proteins from diverse papillomaviruses self-associate both in vitro and in vivo.papillomavirus e6 oncoproteins bind and often provoke the degradation of many cellular proteins important for the control of cell proliferation and/or cell death. structural studies on e6 proteins have long been hindered by the difficulties of obtaining highly concentrated samples of recombinant e6. here, we show that recombinant e6 proteins from eight human papillomavirus strains and one bovine papillomavirus strain exist as oligomeric and multimeric species. these species were characterized us ...201019917295
mutations in sensor 1 and walker b in the bovine papillomavirus e1 initiator protein mimic the nucleotide-bound state.viral replication initiator proteins are multifunctional proteins that utilize atp binding and hydrolysis by their aaa+ modules for multiple functions in the replication of their viral genomes. these proteins are therefore of particular interest for understanding how aaa+ proteins carry out multiple atp driven functions. we have performed a comprehensive mutational analysis of the residues involved in atp binding and hydrolysis in the papillomavirus e1 initiator protein based on the recent struc ...201019939914
interaction of the betapapillomavirus e2 tethering protein with mitotic chromosomes.during persistent papillomavirus infection, the viral e2 protein tethers the viral genome to the host cell chromosomes, ensuring maintenance and segregation of the viral genome during cell division. however, e2 proteins from different papillomaviruses interact with distinct chromosomal regions and targets. the tethering mechanism has been best characterized for bovine papillomavirus type 1 (bpv1), where the e2 protein tethers the viral genome to mitotic chromosomes in complex with the cellular b ...201019846509
generation of a tumor vaccine candidate based on conjugation of a muc1 peptide to polyionic papillomavirus virus-like particles.virus-like particles (vlps) are promising vaccine technology due to their safety and ability to elicit strong immune responses. chimeric vlps can extend this technology to low immunogenicity foreign antigens. however, insertion of foreign epitopes into the sequence of self-assembling proteins can have unpredictable effects on the assembly process. we aimed to generate chimeric bovine papillomavirus (bpv) vlps displaying a repetitive array of polyanionic docking sites on their surface. these vlps ...201020652244
partial sequence analysis of the l1 gene of bovine papillomavirus type 1 detected by pcr with my09/my11 primers in equine sarcoids in poland.bpv-1 is now recognized as a main etiological agent of equine sarcoids. the etiopathogenesis of the equine sarcoids is equivocal and is not yet fully understood. the aim of the present study was to analyse a partial sequence of the l1 gene of bpv associated with equine sarcoids in polish horses. after clinical diagnosis, 40 skin lesions obtained from 29 horses were collected. the amplicons of a fragment of bpv l1 dna were detected using pcr with my09/my11 primers in 31 specimens. all of them wer ...201020731177
effective formation of the segregation-competent complex determines successful partitioning of the bovine papillomavirus genome during cell division.effective segregation of the bovine papillomavirus type 1 (bpv1), epstein-barr virus (ebv), and kaposi's sarcoma-associated human herpesvirus type 8 (kshv) genomes into daughter cells is mediated by a single viral protein that tethers viral genomes to host mitotic chromosomes. the linker proteins that mediate bpv1, ebv, and kshv segregation are e2, lana1, and ebna1, respectively. the n-terminal transactivation domain of bpv1 e2 is responsible for chromatin attachment and subsequent viral genome ...201020810736
prevalence of bpv genotypes in a german cowshed determined by a novel multiplex bpv genotyping assay.bovine papillomaviruses (bpv) induce benign tumours of the cutaneous or mucosal epithelia in cattle, but are also involved in the development of cancer of the urinary bladder and of the upper gastrointestinal tract. current bpv genotyping assays employ techniques developed originally for the detection of human papillomaviruses. these methods rely on consensus pcr amplification and subsequent sequencing and are cumbersome and limited in their analytic sensitivity to detect bpv, especially in mult ...201020816698
structural role of the conserved cysteines in the dimerization of the viral transmembrane oncoprotein e5.the e5 oncoprotein is the major transforming protein of bovine papillomavirus type 1. this 44-residue transmembrane protein can interact with the platelet-derived growth factor receptor β, leading to ligand-independent activation and cell transformation. for productive interaction, e5 needs to dimerize via a c-terminal pair of cysteines, though a recent study suggested that its truncated transmembrane segment can dimerize on its own. to analyze the structure of the full protein in a membrane env ...201020858420
prevalence of bovine papillomavirus and treponema dna in bovine digital dermatitis lesions.bovine digital dermatitis (bdd) is a common infectious foot disease whose aetiology is not fully understood. its origin is thought to be multifactorial, with treponemes being involved. using pcr-based techniques, bdd samples from 45 affected cows and intact skin from 8 bdd-affected and 33 healthy cows were assessed for the presence of bovine papillomavirus and treponema dna. bpv dna (mainly bpv-1/2) was detected in 22% of lesions and one skin sample from affected animals, and in 15% (bpv-1/-2) a ...201020875931
the search for an optimal dna, rna, and protein detection by in situ hybridization, immunohistochemistry, and solution-based methods.clinical trials and correlative laboratory research are increasingly reliant upon archived paraffin-embedded samples. therefore, the proper processing of biological samples is an important step to sample preservation and for downstream analyses like the detection of a wide variety of targets including micro rna, dna and proteins. this paper analyzed the question whether routine fixation of cells and tissues in 10% buffered formalin is optimal for in situ and solution phase analyses by comparing ...201020888418
human papillomavirus e2 protein with single activation domain initiates hpv18 genome replication, but is not sufficient for long-term maintenance of virus genome.the papillomavirus life cycle is regulated by a family of proteins encoded by the e2 open reading frame; e2 proteins regulate viral gene expression, dna replication and genome maintenance. we have previously shown that the bovine papillomavirus (bpv1) full-length e2 protein forms heterodimers with repressor forms of e2, and these e2 heterodimers serve as activators of transcription and replication during the viral life cycle. in the present study, using the single-chain e2 heterodimer as a model ...201020940072
bovine papillomavirus e7 oncoprotein binds to p600 in naturally occurring equine sarcoids.studies regarding the functions of the bovine papillomavirus (bpv) e7 oncoprotein in vivo are lacking and no e7-mediated mechanism underlying mesenchymal carcinogenesis is known. here, we show that the interaction between the 600 kda retinoblastoma protein-associated factor (p600) and bpv e7, described in vitro in cultured cells, takes place in vivo in naturally occurring equine sarcoids. in these cancers we detect the expression of e7 and p600, and demonstrate that e7 and p600 co-localize and p ...201020965990
towards a structural understanding of the smallest known oncoprotein: investigation of the bovine papillomavirus e5 protein using solution-state nmr.the homodimeric e5 protein from bovine papillomavirus activates the platelet-derived growth factor β receptor through transmembrane (tm) helix-helix interactions leading to uncontrolled cell growth. detailed structural information for the e5 dimer is essential if we are to uncover its unique mechanism of action. in vivo mutagenesis has been used to identify residues in the tm domain critical for dimerization, and we previously reported that a truncated synthetic e5 peptide forms dimers via tm do ...201021073859
bovine papillomavirus dna can be detected in keratinocytes of equine sarcoid tumors.bovine papillomavirus (bpv)-1 and -2 is linked to equine sarcoids, a commonly observed skin tumor in horses that is of considerable veterinary importance. previous studies using in situ hybridization have detected bpv dna only in fibroblasts and not in keratinocytes of sarcoids. in contrast, normal equine skin latently infected with bpv shows a dysplastic epithelium without dermal changes, similar to lesions induced by other papillomavirus types infecting the epithelium. the first goal of our st ...201021095508
construction and maintenance of randomized retroviral expression libraries for transmembrane protein engineering.genetic selection from libraries expressing proteins with randomized amino acid segments is a powerful approach to identify proteins with novel biological activities. here, we assessed the utility of deep dna sequencing to characterize the composition, diversity, size and stability of such randomized libraries. we used 454 pyrosequencing to sequence a retroviral library expressing small proteins with randomized transmembrane domains. despite the potential for unintended random mutagenesis during ...201021149273
different contribution of bovine papillomavirus type 1 oncoproteins to the transformation of equine fibroblasts.equine sarcoids represent the most common skin tumours in equids worldwide, characterized by localized invasion, rare regression and high recurrence following surgical intervention. bovine papillomavirus type 1 (bpv-1) and less commonly bpv-2 are now widely recognized as the causative agents of the disease. fibroblasts isolated from sarcoids are highly invasive. invasion is associated with a high level of viral gene expression and matrix metalloproteinase upregulation. however, it remains unclea ...201021177927
epidemiology of equine sarcoids in horses in western canada.sarcoids are the most common tumor of the equine skin but only 1 study describing the epidemiology of sarcoids in canadian horses has been published. the records of 5 veterinary diagnostic laboratories in western canada were searched to identify submissions of sarcoids from horses. the submission records and diagnostic reports of 802 separate submissions of equine sarcoids were reviewed for age, breed, and gender of the horse and the number, location, and clinical type of sarcoid. from these rec ...201021197201
strong oligomerization behavior of pdgfbeta receptor transmembrane domain and its regulation by the juxtamembrane regions.the platelet-derived growth factor beta-receptor (pdgfbetar) represents an important subclass of receptor tyrosine kinase (rtk) thought to be activated by ligand-induced dimerization. interestingly, the receptor is also activated by the bovine papillomavirus e5 oncoprotein, an interaction involving the transmembrane domains of both proteins and resulting in constitutive downstream signalling. this unique mode of activation along with emerging data for other rtks raises important questions about ...201020036637
molecular identification of bovine papillomaviruses associated with cutaneous warts in southern brazil.bovine papillomaviruses (bpvs) are widespread pathogens mainly associated with benign, self-limiting, cutaneous lesions (warts). at least 8 viral types, defined by serology or nucleotide sequences of the l1 gene, have been identified to date. different serotypes are associated with the specific type and morphology of the lesion and with particular geographical regions. this article describes the molecular identification of papillomaviruses from brazilian cattle (n = 48) and horses (n = 1) throug ...201020622233
phylogenetic position of an uncharacterized brazilian strain of bovine papillomavirus in the genus xipapillomavirus based on sequencing of the l1 open reading frame.the use of pcr assays with degenerate primers has suggested the existence of numerous as yet uncharacterized bovine papillomaviruses (bpv). despite the endemic nature of bpv infections, the identification of bpv types in brazilian cattle is still only sporadic. however, in a recent analysis of a partial segment of the l1 gene, we observed notable diversity among the bpv types detected. the aim of this study was to determine the phylogenetic position of the previously identified wild strain bpv/b ...201021637585
bovine papillomavirus type 1 and equus caballus papillomavirus 2 in equine squamous cell carcinoma of the head and neck in a connemara mare.in january 2010, 18 months after excision of an ocular squamous cell carcinoma (scc), a connemara mare presented with anorexia and periorbital/parotideal lesions. post mortem examination revealed these lesions as forming one entity, with 2 additional growths in the retropharyngeal region and the left jugular groove, respectively. the lesions were confirmed histopathologically as sccs. using pcr, peripheral blood mononuclear cells (pbmcs) from 2008 and 2010, tumour tissue, intact skin and vulval ...201121668491
preliminary assessment of binary ethylenimine inactivated and saponized cutaneous warts (bpv-2) therapeutic vaccine for enzootic bovine haematuria in hill cows.a preliminary therapeutic vaccine trial was conducted in hill cows to evaluate the therapeutic potential of binary ethylenimine (bei) inactivated and saponized bovine papillomavirus-2 (bpv-2) for enzootic bovine haematuria (ebh). although the vaccine failed to show favorable clinical vaccine results in treatment of ebh affected cows at 120 days post-vaccination but immunopathological responses were encouraging. a significant difference was observed in humoral (against brucella abortus strain 19s ...201121803104
detection and quantification of bovine papilloma virus type 2 (bpv-2) by real-time pcr in urine and urinary bladder lesions in enzootic bovine haematuria (ebh)-affected cows.this study was conducted with the objectives of detecting bovine papillomavirus type 2 (bpv-2) in urine samples and urinary bladder lesions in bovines using polymerase chain reaction (pcr) and real-time pcr-based molecular diagnostic tests, and quantifying bpv-2 in urinary bladder lesions especially in enzootic bovine haematuria (ebh)-affected animals. bpv-2 viral dna was detected in urine samples (50%) and urinary bladder tissue (68.6%). cloning and sequencing results showed a close homology wi ...201121797988
strategies for bacterial expression of protein-peptide complexes: application to solubilization of papillomavirus e6.e6 is a small oncoprotein involved in tumorigenesis induced by papillomaviruses (pvs). e6 often recognizes its cellular targets by binding to short motifs presenting the consensus lxxll. e6 proteins have long resisted structural analysis. we found that bovine papillomavirus type 1 (bpv1) e6 binds the n-terminal lxxll motif of the cellular protein paxillin with significantly higher affinity as compared to other e6/peptide interactions. although recombinant bpv1 e6 was poorly soluble in the free s ...201121777678
upregulation of equine mmp-1 by bpv-1 is through the transcription factor ap-1.equine sarcoids represent the most common skin tumours in equids worldwide, characterised by extensive invasion and infiltration of lymphatics, rare regression and high recurrence after surgical intervention. bovine papillomavirus type-1 (bpv-1) activity is necessary for the transformation phenotype of equine fibroblasts. among the many changes induced by bpv-1, mmp-1 upregulation contributes to the invasiveness of equine fibroblasts. however it is yet unknown how bpv-1 proteins regulate equine ...201121775582
targeting the human papillomavirus e6 and e7 oncogenes through expression of the bpv1 e2 protein stimulates cellular motility.expression of the high risk human papillomavirus (hpv) e6 and e7 oncogenes is essential for the initiation and maintenance of cervical cancer. the repression of both was previously shown to result in activation of their respective tumor suppressor targets p53 and prb, and subsequent senescence induction in cervical cancer cells. consequently, viral oncogene suppression is a promising approach for the treatment of hpv positive tumors. one well established method of e6/e7 repression involves the r ...201121835799
inoculation of young horses with bpv-1 virion leads to early infection of peripheral blood mononuclear cells (pbmc) prior to pseudo-sarcoid formation.bovine papillomavirus types 1 and 2 (bpv-1, bpv-2) are known to induce common equine skin tumours termed sarcoids. recently, we have demonstrated that vaccination with bpv-1 virus-like particles (vlp) is safe and highly immunogenic in horses. to establish a bpv-1 challenge model for evaluation of the protective potential of bpv-1 vlps, 4 foals were intradermally injected with infectious bpv-1 virion, viral genome-based and control inocula, and daily monitored for tumour development. blood was ta ...201121715602
detection of bovine papillomavirus type 2 dna in commercial frozen semen of bulls (bos taurus).papillomaviruses are found in epithelial lesions and are linked to different carcinogenic processes in humans and other animals. although bovine papillomavirus (bpv) has been characterized as epitheliotropic, the presence of viral dna has been detected in other sample types, including fresh semen. the aim of this study was to evaluate the presence of bpv dna in spermatozoa and seminal plasma samples of commercial frozen semen taken from bulls (bos taurus) and its effects on semen function. pcr a ...201122172321
a multimeric l2 vaccine for prevention of animal papillomavirus infections.it is unclear what level of neutralizing antibody is sufficient to protect cattle from experimental bovine papillomavirus type 4 (bpv4) challenge. markedly lower, and often undetected, serum neutralizing antibody titers were associated with protection in cattle vaccinated with bpv4 l2 as compared to l1 vlp. we hypothesized that vaccination with concatemers of the n-terminal protective epitopes of l2 derived from multiple animal papillomavirus types would enhance the breadth and strength of immun ...201121920572
detection and characterisation of papillomavirus in skin lesions of giraffe and sable antelope in south africa.papillomavirus was detected electron microscopically in cutaneous fibropapillomas of a giraffe (giraffa camelopardalis) and a sable antelope (hippotragus niger). the virus particles measured 45 nm in diameter. histopathologically, the lesions showed histopathological features similar to those of equine sarcoid as well as positive immunoperoxidase-staining of tissue sections for papillomavirus antigen. polymerase chain reaction (pcr) detected bovine papillomavirus (bpv) dna. bovine papillomavirus ...201122135920
pathology and immunohistochemistry of papillomavirus-associated cutaneous lesions in cape mountain zebra, giraffe, sable antelope and african buffalo in south africa.skin lesions associated with papillomaviruses have been reported in many animal species and man. bovine papillomavirus (bvp) affects mainly the epidermis, but also the dermis in several species including bovine, the best-known example being equine sarcoid, which is associated with bvp types 1 and 2. this publication describes and illustrates the macroscopic and histological appearance of bpv-associated papillomatous, fibropapillomatous or sarcoid-like lesions in cape mountain zebra (equus zebra ...201122135923
molecular and immunohistochemical distinction of equine sarcoid from schwannoma.ten equine skin tumors that had been classified as schwannomas on routine histological examination were analyzed by polymerase chain reaction for bovine papillomavirus dna. all 10 were positive for bovine papillomavirus 1 or 2, and all 10 were immunohistochemically negative for s-100 protein and strongly positive for vimentin. nine tumors were moderately positive for laminin and 8, for smooth muscle actin. five tumors were variably and weakly positive for type iv collagen. the lack of s-100 prot ...201120634412
expression of gap junction protein connexin 43 in bovine urinary bladder tumours.the aetiopathogenesis of urinary bladder tumours in cattle involves prolonged ingestion of bracken fern and infection by bovine papillomavirus types 1 or 2 (bpv-1/2). the oncogenic activity of bpv is largely associated with the major oncoprotein e5. gap junctions are the only communicating junctions found in animal tissues and are composed of proteins known as connexins. alterations in connexin expression have been associated with oncogenesis. the present study investigated biochemically and imm ...201120643416
localization of bovine papillomavirus in equine sarcoids and inflammatory skin conditions of horses using laser microdissection and two forms of dna amplification.equine sarcoids are the most common tumor of horses. bovine papillomavirus (bpv) has been suggested as the cause of sarcoids. studies have shown that bpv is present in swabs or biopsies from nonsarcoid-bearing equine skin. skin biopsies from a variety of different conditions and normal skin from horses with no reported history of sarcoids were examined by polymerase chain reaction (pcr) for the presence of bpv, which was found in all different types of skin conditions as well as normal skin. for ...201122362933
phylogenetic analysis of bovine papillomavirus e5 detected in equine sarcoids in poland.the aim of the study was to analyse a part of the sequence of the e5 gene of bovine papillomaviruses (bpv) associated with equine sarcoids in polish horses. samples of 40 skin lesions obtained from 29 horses were collected for molecular examination. the pcr amplicons of bpv dna were detected in 38 specimens. after phylogenetic analysis 37 specimens were recognized as bpv-1 and one as bpv-2. phylogenetic analysis has allowed the classification of the amplicons into two phylogenetic groups (a1,) a ...201122439338
pathological study of non-neoplastic urinary bladder lesions in cattle and buffaloes: a preliminary report.a total of 236 urinary bladders (94 cattle and 142 buffaloes) collected from bareilly, uttar pradesh, india, were studied for spontaneous lesions. these adult animals belonged to institute's organized dairy farm and rural areas in the rohilkhand region of uttar pradesh. grossly, congestion, hemorrhages, and cystoliths in urinary bladders were diagnosed. histopathologically, the major conditions diagnosed were acute cystitis, 44 (18.64%), including, congestion, hemorrhages, sub-acute cystitis; ch ...201121935661
Characterization of novel bovine papillomavirus type 12 (BPV-12) causing epithelial papilloma.Bovine papillomavirus type 12 (BPV-12, putative type BAA1) was detected in epithelial papilloma located on the tongue of an infected cow. Then, the whole genome was sequenced, and phylogenetic analysis illustrated that it should be classified as a member of the genus Xipapillomavirus. The viral genome is 7197 base pairs in length and contains five early ORFs (E1, E2, E4, E7 and E8), three late ORFs (L1, L2 and L3), and a long control region that possesses replication regulatory elements. Meanwhi ...201122033594
cytogenetic studies in peripheral blood of bovines afflicted by papillomatosis.ten types of bovine papillomavirus (bpv) have been described and there are reports of viral transmission via blood. the presence of viral dna in lymphocytes was described to be associated with chromosome instability in these cells. this study presents an evaluation of chromosome instability in short-term peripheral lymphocyte cultures from cows presenting skin papillomatosis, compared with asymptomatic infected animals and non-infected healthy bovines. in a total of 2203 cells, 918 (42%) showed ...201122077407
smurf2 alters bpv1 trafficking and decreases infection.papillomavirus capsid proteins l1 and l2 mediate virion attachment, internalization and trafficking. in our studies of the capsid proteins, we identified an interaction of l2 with the e3 ligase smad ubiquitin regulatory factor 2 (smurf2). smurf2 expression alters bpv1 virion trafficking and l2 protein levels. using bpv1 pseudovirions (psvs) containing a gfp or dsred transgene encapsidated by l1 and l2 proteins, our data showed that although only bpv1 l2 interacts with smurf2, both l1 and l2 leve ...201121318310
detection of a novel bovine papillomavirus type 11 (bpv-11) using xipapillomavirus consensus polymerase chain reaction primers.polymerase chain reaction-based bovine papillomavirus (bpv) detection methods using a combination of two primer sets, subaup/subadw and subbup/subbdw, have enabled the broad-spectrum detection of most characterized bpv types. these methods were used to detect the partial l1 nucleotide sequence of bpv types from 167 cutaneous warts in cattle. three potentially new viruses were detected using subbup/subbdw primer sets. the partial nucleotide sequences of these viruses were most similar to bpv-4, - ...201121424729
p38 mapk is crucial for bpv-1 transformation of equine fibroblasts.equine sarcoids represent the most common skin tumours in equids worldwide, characterised by extensive invasion and infiltration of lymphatics, rare regression and high recurrence after surgical intervention. bovine papillomavirus type-1 (bpv-1) and less commonly bpv-2 are the causing agents of the diseases. it has been demonstrated that bpv-1 viral gene expression is necessary for maintaining the transformation phenotype. however the underlying mechanism for bpv-1 transformation remains largely ...201121471309
characterization of complete genomes of camelus dromedarius papillomavirus type 1 and 2.camel papillomatosis has been previously described but the genome of the suspected papillomavirus (pv) has not been identified. an outbreak of papillomatosis occurred in a dromedary farm of 55 animals in sudan during august 2009. the disease was only present in young animals about 3-7 months old, of which 44 % (11/25) were affected with lesions mainly on the lips and lower jaw. here we report for the first time the complete genomes of camelus dromedarius papillomavirus type 1 (cdpv1) and 2 (cdpv ...201121471319
in vivo analysis of the cell cycle dependent association of the bovine papillomavirus e2 protein and chlr1.it has been shown that the genomes of episomally maintained dna viruses are tethered to host cell chromosomes during cell division, facilitating maintenance in dividing cells. the papillomavirus e2 protein serves this mechanism of viral genome persistence by simultaneously associating with chromatin and the viral genome during mitosis. several host cell proteins are reported to be necessary for the association of e2 with chromatin including the cohesion establishment factor chlr1. here we use fl ...201121489590
successful treatment of equine sarcoids by topical aciclovir application.based on the anecdotally reported eradication of a sarcoid using aciclovir cream, the curative potential of this ointment was investigated in 22 sarcoid-affected horses referred to the equine clinic tillysburg, austria, between 2006 and 2009. sarcoid disease was diagnosed by clinical examination and bovine papillomavirus types 1 and 2 from intact skin and tumour tissue. as nine horses had more than one lesion, a total of 47 sarcoids were treated by daily topical application of aciclovir 5 per ce ...201121493530
peripheral blood mononuclear cells are additional sites of productive infection of bovine papillomavirus type 2.bovine papillomavirus type 2 (bpv-2) is an oncogenic virus infecting both epithelial and mesenchymal cells. its life cycle, similar to other papillomaviruses, appears to be linked to epithelial differentiation. human and bovine papillomaviruses have been shown to circulate as a latent, episomal form in peripheral blood mononuclear cells (pbmc); therefore, it is believed that blood cells, like all mesenchymal cells, function as nonpermissive carriers. for the first time in veterinary and comparat ...201121525209
activated platelet-derived growth factor β receptor and ras-mitogen-activated protein kinase pathway in natural bovine urinary bladder carcinomas.bovine papillomavirus types 1 or 2 (bpv-1/2) are involved in the aetiopathogenesis of bovine urinary bladder cancer. bpv-1/2 e5 activates the platelet-derived growth factor β receptor (pdgfβr). the aim of this study was to analyse the ras/mitogen-activated protein kinase (mapk) pathway in relation to activation of pdgfβr in natural bovine urinary bladder carcinomas. co-immunoprecipitation and western blot analysis demonstrated that recruitment of growth factor receptor bound protein 2 (grb-2) an ...201121546288
consistent detection of bovine papillomavirus in lesions, intact skin and peripheral blood mononuclear cells of horses affected by hoof canker.equine hoof canker is a chronic proliferative pododermatitis of as yet unknown aetiology. like equine sarcoid disease, canker is a therapy-resistant disorder characterised by hyperkeratosis, acanthosis and a marked tendency to recur.201121592216
morphological factors as indicators of malignancy of squamous cell carcinomas in cattle exposed naturally to bracken fern (pteridium aquilinum).squamous cell carcinomas (sccs) of the upper digestive tract (udt) of cattle have been associated with chronic bracken fern (pteridium aquilinum) toxicity and infection with bovine papillomavirus type-4. these tumours share some morphological similarities with human head and neck sccs. in this study, morphological changes were correlated with the biological behaviour of 40 alimentary sccs in cattle grazing on pastures with high bracken content. the majority of sccs were localized to the cranial ...201120542519
association of bovine papillomavirus type 2 (bpv-2) and urinary bladder tumours in cattle from the azores archipelago.urinary bladder tumours in cattle are caused by chronic ingestion of bracken fern and bpv-1/2 infection. the objective of the present study was to assess if bpv-2 was present in urinary bladder lesions from cattle with chronic enzootic haematuria (ceh) from the azores archipelago (portugal), in order to gain further information regarding the epidemiologic distribution of this virus. samples were analysed using pcr specific primers for bpv-2 dna and an immunohistochemistry for bpv e5 oncoprotein ...201120189209
cutaneous papillomavirus e6 oncoproteins associate with maml1 to repress transactivation and notch signaling.papillomavirus e6 oncoproteins associate with lxxll motifs on target cellular proteins to alter their function. using a proteomic approach, we found the e6 oncoproteins of cutaneous papillomaviruses bovine papillomavirus type 1 (bpv-1) e6 and human papillomavirus (hpv) types 1 and 8 (1e6 and 8e6) associated with the maml1 transcriptional co-activator. all three e6 proteins bind to an acidic lxxll motif at the carboxy-terminus of maml1 and repress transactivation by maml1. maml1 is best known as ...201222249263
co-infection of bovine papillomavirus and feline-associated papillomavirus in bovine cutaneous warts.the diversity of papillomavirus (pv) found in bovine cutaneous warts from brazilian cattle was evaluated using the pcr technique with the utilization of consensus primers my09/11 and by pcr using bovine papillomavirus (bpv) type-specific primers followed by sequencing. eleven cutaneous warts from 6 cattle herds were selected. six warts were positive for the presence of pv. the presence of bpv types 1, 2, 3, 6 and feline sarcoid-associated pv (fesarpv) in cutaneous wart lesions, as well as the pr ...201222273488
Primary human cervical carcinoma cells require human papillomavirus E6 and E7 expression for ongoing proliferation.Repression of human papillomavirus (HPV) E6 and E7 oncogenes in established cervical carcinoma cell lines causes senescence due to reactivation of cellular tumor suppressor pathways. Here, we determined whether ongoing expression of HPV16 or HPV18 oncogenes is required for the proliferation of primary human cervical carcinoma cells in serum-free conditions at low passage number after isolation from patients. We used an SV40 viral vector expressing the bovine papillomavirus E2 protein to repress ...201222056390
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