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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
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
a novel two-step transcriptional activation system for gene therapy directed toward epithelial cells.the two-step transcriptional activation (tsta) mechanism in gene therapy amplifies cell type-specific promoter activity, allowing for increased levels of gene expression in target tissues. in this system, the specific promoter drives expression of a strong transcriptional activator that binds to dna target sequences located upstream from a second promoter controlling the expression of the therapeutic gene. the majority of previous studies have exploited a fusion between the dna binding domain of ...200919952120
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
cell-type specific transcriptional activities among different papillomavirus long control regions and their regulation by e2.this study systematically examined the viral long control region (lcr) activities and their responses to e2 for human papillomavirus (hpv) types 11, 16, and 18 as well as bovine papillomavirus 1 (bpv1) in a number of different cell types, including human cervical cancer cell lines, human oral keratinocytes, bj fibroblasts, as well as cv1 cells. the study revealed cell- and virus-type specific differences among the individual lcrs and their regulation by e2. in addition, the integration of the lc ...200919836046
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
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
chromatin adaptor brd4 modulates e2 transcription activity and protein stability.brd4 is a chromatin adaptor containing tandem bromodomains binding to acetylated histone h3 and h4. although brd4 has been implicated in the transcriptional control of papillomavirus-encoded e2 protein, it is unclear how brd4 regulates e2 function and whether the involvement of brd4 in transactivation and transrepression is common to different types of e2 proteins. using dnase i footprinting performed with in vitro reconstituted human papillomavirus (hpv) chromatin and nucleosome-free dna templa ...200919038968
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
can established cultured papilloma cells harbor bovine papillomavirus?papillomaviruses have been reported to be very difficult to grow in cell culture. also, there are no descriptions of cell cultures from lesions of bovine cutaneous papillomatosis, with identification of different bovine papilloma virus (bpv) dna sequences. in the present report, we describe primary cell cultures from samples of cutaneous lesions (warts). we investigated the simultaneous presence of different bpv dna sequences, comparing the original lesion to different passages of the cell cultu ...200819048490
detection of bovine papillomavirus type 2 in the peripheral blood of cattle with urinary bladder tumours: possible biological role.bovine papillomavirus type 2 (bpv-2) infection has been associated with urinary bladder tumours in adult cattle grazing on bracken fern-infested land. in this study, we investigated the simultaneous presence of bpv-2 in whole blood and urinary bladder tumours of adult cattle in an attempt to better understand the biological role of circulating bpv-2. peripheral blood samples were collected from 78 cattle clinically suffering from a severe chronic enzootic haematuria. circulating bpv-2 dna was de ...200819008389
fibropapilloma of the glans penis in a horse.an 18-year-old arabian stallion was presented for recent onset of stranguria. physical examination of the distal portion of the glans penis revealed multiple, smooth, glistening, grayish-pink, variably sized, exophytic, nodular masses circumferentially surrounding the external urethral orifice. partial penile amputation was performed, and the entire specimen was submitted for histological evaluation. microscopically, the masses consisted of abundant amounts of loosely arranged fibrovascular stro ...200818987237
association of bovine papillomavirus type-2 and urinary bladder tumours in cattle from romania.in cattle, bracken fern toxicity is characterized by the presence of haematuria and tumours of the urinary bladder of both epithelial and mesenchymal origin. this syndrome is known as chronic enzootic hematuria (ceh) and is also present in romania. from january 2006 to april 2007, 90 urinary bladders from slaughtered cows originating from hill-mountain area of neamt county (romania), where ceh is endemic, were collected. all samples were histologically examined and bovine papillomavirus type 2 ( ...200818031773
establishment and characterization of equine fibroblast cell lines transformed in vivo and in vitro by bpv-1: model systems for equine sarcoids.it is now widely recognized that bpv-1 and less commonly bpv-2 are the causative agents of equine sarcoids. here we present the generation of equine cell lines harboring bpv-1 genomes and expressing viral genes. these lines have been either explanted from sarcoid biopsies or generated in vitro by transfection of primary fibroblasts with bpv-1 dna. previously detected bpv-1 genome variations in equine sarcoids are also found in sarcoid cell lines, and only variant bpv-1 genomes can transform equi ...200818191170
multiple glomus tumors of the urinary bladder in a cow associated with bovine papillomavirus type 2 (bpv-2) infection.we report a case of multiple glomus tumors associated with bovine papillomavirus type 2 (bpv-2) infection in the urinary bladder of a 13-year-old cow suffering from severe chronic enzootic hematuria. macroscopically, multiple submucosal reddish nodules were seen swelling the vesical mucosa. histologically, neoplastic proliferation was characterized by the presence of numerous blood vessels. these were lined by normal endothelial cells surrounded by round epithelioid cells with central nuclei, pr ...200818192572
melanosis of the urinary bladder in a cow.melanosis of the urinary bladder is a very rare condition characterized by an abnormal black or brownish-black pigmentation of the organ. the pigmentary disorder can involve both the urothelial cell layers and/or the submucosa. the biologic potential of the melanosis of urinary bladder remains unknown because only a few cases have been reported in medical literature. so far melanosis of the urinary bladder is not known to occur in cattle. here we describe the first case of melanosis of the urina ...200818192574
identification of a nuclear export signal sequence for bovine papillomavirus e1 protein.recent studies have demonstrated nuclear export by papillomavirus e1 proteins, but the requisite export sequence(s) for bovine papillomavirus (bpv) e1 were not defined. in this report we identify three functional nuclear export sequences (nes) present in bpv e1, with nes2 being the strongest in reporter assays. nuclear localization of bpv1 e1 was modulated by over- or under-expression of crm1, the major cellular exportin, and export was strongly reduced by the crm1 inhibitor, leptomycin b, indic ...200818201744
a dna-binding activity in bpv initiator protein e1 required for melting duplex ori dna but not processive helicase activity initiated on partially single-stranded dna.the papillomavirus replication protein e1 assembles on the viral origin of replication (ori) as a series of complexes. it has been proposed that the ori dna is first melted by a head-to-tail double trimer of e1 that evolves into two hexamers that encircle and unwind dna bi-directionally. here the role of a conserved lysine residue in the smaller tier or collar of the e1 helicase domain in ori processing is described. unlike the residues of the aaa+ domain dna-binding segments (beta-hairpin and h ...200818267969
pathological studies on bovine papilloma virus-fern interaction in hamsters.early pathological changes of bovine papilloma virus (bpv-2)-fern (pteridium aquilinum and onychium contiguum fern) interaction in hamsters were studied. in bracken-exposed cattle, bpv induces malignancy in gastrointestinal and urinary bladder mucosa. cutaneous warts were transmitted successfully in hamsters approximately after 3 months post inoculation while urinary bladder tumour of enzootic bovine haematuria cases were not transmitted. histologically, tumour was diagnosed as fibroma. onychium ...200818335807
transforming signals resulting from sustained activation of the pdgfbeta receptor in mortal human fibroblasts.the platelet-derived growth factor beta receptor (pdgfbetar) plays an important role in proliferation and motility of fibroblasts. we have been investigating the effects of sustained pdgfbetar activation in mortal human diploid fibroblasts (hdfs), which are typically difficult to transform. we have previously shown that the bovine papillomavirus e5 protein, through its ability to crosslink and constitutively activate the pdgfbetar, induces morphological transformation, enhanced growth and loss o ...200818349076
transformation by bovine papillomavirus type 1 e6 requires paxillin.papillomavirus e6 proteins are adapters that change the function of cellular regulatory proteins. the bovine papillomavirus type 1 e6 (be6) binds to lxxll peptide sequences termed ld motifs (consensus sequence ldxllxxl) on the cellular protein paxillin that is a substrate of src and focal adhesion kinases. anchorage-independent transformation induced by be6 required both paxillin and be6-binding ld motifs on paxillin but was independent of the major tyrosine phosphorylation sites of paxillin. th ...200818385245
a subset of equine sarcoids harbours bpv-1 dna in a complex with l1 major capsid protein.bovine papillomavirus type 1 or 2 (bpv-1, bpv-2) are accepted causal factors in equine sarcoid pathogenesis. whereas viral genomes are consistently found and expressed within lesions, intact virions have never been detected, thus permissiveness of sarcoids for bpv-1 replication remains unclear. to reassess this issue, an immunocapture pcr (ic/pcr) was established using l1-specific antibodies to capture l1-dna complexes followed by amplification of the viral genome. following validation of the as ...200818395238
bovine papillomavirus type 1: from clathrin to caveolin.viruses may infect cells through clathrin-dependent, caveolin-dependent, or clathrin- and caveolin-independent endocytosis. bovine papillomavirus type 1 (bpv1) entry into cells has been shown to occur by clathrin-dependent endocytosis, a pathway that involves the formation of clathrin-coated pits and fusion to early endosomes. recently, it has been demonstrated that the closely related jc virus can enter cells in clathrin-coated vesicles and subsequently traffic to caveolae, the organelle where ...200818417596
virus-like display of a neo-self antigen reverses b cell anergy in a b cell receptor transgenic mouse model.the ability to distinguish between self and foreign ags is a central feature of immune recognition. for b cells, however, immune tolerance is not absolute, and factors that include ag valency, the availability of t help, and polyclonal b cell stimuli can influence the induction of autoantibody responses. here, we evaluated whether multivalent virus-like particle (vlp)-based immunogens could induce autoantibody responses in well-characterized transgenic (tg) mice that express a soluble form of he ...200818424700
transcriptional changes induced by bovine papillomavirus type 1 in equine fibroblasts.bovine papillomavirus type 1 (bpv-1) and, less commonly, bpv-2 are associated with the pathogenesis of common equine skin tumors termed sarcoids. in an attempt to understand the mechanisms by which bpv-1 induces sarcoids, we used gene expression profiling as a screening tool to identify candidate genes implicated in disease pathogenesis. gene expression profiles of equine fibroblasts transformed by bpv-1 experimentally or from explanted tumors were compared with those of control equine fibroblas ...200818434409
molecular analysis of the fragile histidine triad (fhit) tumor suppressor gene in vesical tumors of cattle with chronic enzootic hematuria (ceh).the fhit (fragile histidine triad) gene is a tumor suppressor gene known to be inactivated in many tumors including bladder tumors and is spanning fra3b, a very active common fragile site in the human genome. we have recently isolated the bovine gene, and the aim of this study was to test whether fhit presents altered expression patterns in vesical tumors of cattle with ceh (chronic enzootic hematuria). ceh is a common syndrome affecting mediterranean cattle: clastogenic, mutagenic and canceroge ...200818467844
peripheral blood mononuclear cells represent a reservoir of bovine papillomavirus dna in sarcoid-affected equines.bovine papillomaviruses of types 1 and 2 (bpv-1 and -2) chiefly contribute to equine sarcoid pathogenesis. however, the mode of virus transmission and the presence of latent infections are largely unknown. this study established a pcr protocol allowing detection of <or=10 copies of the bpv-1/-2 genes e5 and l1. subsequent screening of peripheral blood mononuclear cell (pbmc) dna derived from horses with and without bpv-1/2-induced skin lesions demonstrated the exclusive presence of e5, but not l ...200818474554
md simulations of papillomavirus dna-e2 protein complexes hints at a protein structural code for dna deformation.the structural dynamics of the dna binding domains of the human papillomavirus strain 16 and the bovine papillomavirus strain 1, complexed with their dna targets, has been investigated by modeling, molecular dynamics simulations, and nuclear magnetic resonance analysis. the simulations underline different dynamical features of the protein scaffolds and a different mechanical interaction of the two proteins with dna. the two protein structures, although very similar, show differences in the relat ...200818487311
dimerization of the papillomavirus e2 protein is required for efficient mitotic chromosome association and brd4 binding.the e2 proteins of several papillomaviruses link the viral genome to mitotic chromosomes to ensure retention and the efficient partitioning of genomes into daughter cells following cell division. bovine papillomavirus type 1 e2 binds to chromosomes in a complex with brd4, a cellular bromodomain protein. interaction with brd4 is also important for e2-mediated transcriptional regulation. the transactivation domain of e2 is crucial for interaction with the brd4 protein; proteins lacking or mutated ...200818495759
simultaneous presence of bovine papillomavirus and bovine leukemia virus in different bovine tissues: in situ hybridization and cytogenetic analysis.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 stud ...200818561382
identification of unreported putative new bovine papillomavirus types in brazilian cattle herds.the amplification by degenerate primers fap59/fap64 and sequencing allowed the detection of 15 putative new bpv types in cutaneous warts as well as in healthy skin. four of these isolates were recently recognized as new bpv types (bpv-7, -8, -9, and -10) after determination of their complete genome sequences. in brazil, investigations involving the definition of bpv types present in skin warts are still rare. the aim of the current study was to identify the bpv types associated with cutaneous pa ...200818617336
modification of papillomavirus e2 proteins by the small ubiquitin-like modifier family members (sumos).papillomavirus e2 proteins are critical regulatory proteins that function in replication, genome segregation, and viral transcription, including control of expression of the viral oncogenes, e6 and e7. sumoylation is a post-translational modification that has been shown to target and modulate the function of many transcription factors, and we now demonstrate that e2 proteins are sumoylated. both bovine and human papillomavirus e2 proteins bind to the sumo conjugation enzyme, ubc9, and using in v ...200818619639
hpv16 and bpv1 infection can be blocked by the dynamin inhibitor dynasore.the initial entry of papillomaviruses into their target cells has been shown to occur by clathrin-mediated endocytosis and caveolae-mediated endocytosis. these mechanisms entail the formation of nascent-coated vesicles at the plasma membrane. such coated vesicles, clathrin or caveolin, form and pinch-off in a controlled mechanism that involves several proteins including dynamin. dynamin is a gtpase that forms a dynamin ring at the stem connecting the nascent vesicle to the plasma membrane. in a ...200818645330
in vitro dimerization of the bovine papillomavirus e5 protein transmembrane domain.the e5 protein from bovine papillomavirus is a type ii membrane protein and the product of the smallest known oncogene. e5 causes cell transformation by binding and activating the platelet-derived growth factor beta receptor (pdgfbetar). in order to productively interact with the receptor, it is thought that e5 binds as a dimer. however, wild-type e5 and various mutants have also been shown to form trimers, tetramers, and even higher order oligomers. the residues in e5 that drive and stabilize a ...200818672907
lymphoepithelioma-like carcinoma of the urinary bladder in a cow associated with bovine papillomavirus type-2.lymphoepithelioma-like carcinoma (lelca) of the urinary bladder is reported in a 7-year-old cow that had grazed pasture rich in bracken fern and had suffered from severe intermittent haematuria from 3 to 4 years of age. on necropsy examination there were multiple haemorrhagic foci scattered over the mucosal surface of the urinary bladder. microscopically there were nests, cords and sheets of neoplastic cells infiltrating the lamina propria and muscularis propria. these had a syncytial appearance ...200818675990
expression of platelet-derived growth factor-beta receptor and bovine papillomavirus e5 and e7 oncoproteins in equine sarcoid.equine sarcoids are benign fibroblastic skin tumours that are recognized throughout the world. infection with bovine papillomavirus (bpv) types 1 and 2 has been implicated as a major factor in disease development; however, the cellular mechanisms underlying fibroblast transformation remain poorly defined. the present study further characterizes aspects of the association with bpv in 15 equine sarcoids. bpv dna was demonstrated in 12/15 tumours collected from different areas of italy. nine of the ...200818814884
sarcoids in two captive tapirs (tapirus bairdii): clinical, pathological and molecular study.this case report describes for the first time sarcoids in tapirs (tapirus bairdii), namely, a 2-year-old male and a 3.6-year-old female born and housed at the same facility. the male presented with a 3-cm nodular, red, pedunculated, hairless, ulcerated mass on the inner surface of the left pinna. no recurrence or additional growths were present during the 3 years following surgical excision of the mass. the female presented with a similar 2-cm mass on the inner surface of the right pinna, which ...200818817531
bovine papillomaviruses: their role in the aetiology of cutaneous tumours of bovids and equids.bovine papillomavirus (bpv) is perhaps the most extensively studied animal papillomavirus. in cattle bpvs induce benign tumours of cutaneous or mucosal epithelia, called papillomas or warts. cattle papillomas are benign tumours and generally regress without eliciting any serious clinical problems in the host, but occasionally persist and provide the focus for malignant transformation to squamous cell carcinoma, as in the case of cancer of the urinary bladder and cancer of the upper alimentary ca ...200818927950
the regulatory element in the 3'-untranslated region of human papillomavirus 16 inhibits expression by binding cug-binding protein 1.the 3'-untranslated regions (utrs) of human papillomavirus 16 (hpv16) and bovine papillomavirus 1 (bpv1) contain a negative regulatory element (nre) that inhibits viral late gene expression. the bpv1 nre consists of a single 9-nucleotide (nt) u1 small nuclear ribonucleoprotein (snrnp) base pairing site (herein called a u1 binding site) that via u1 snrnp binding leads to inhibition of the late poly(a) site. the 79-nt hpv16 nre is far more complicated, consisting of 4 overlapping very weak u1 bind ...200818042543
immunotherapy of equine sarcoid: dose-escalation trial for the use of chimeric papillomavirus-like particles.equine sarcoids are fibrosarcoma-like skin tumours with a prevalence of approximately 1-2 %. strong evidence exists for a causative role of bovine papillomavirus (bpv) type 1 or type 2 in the development of sarcoids. no effective treatment of equine sarcoid is available and after surgical excision relapse of the tumours is very frequent. we developed chimeric virus-like particles (cvlps) of bpv 1 l1-e7 for the immunotherapy of equine sarcoid. in a phase i clinical trial 12 horses suffering from ...200818089737
vaccination of sarcoid-bearing donkeys with chimeric virus-like particles of bovine papillomavirus type 1.equine sarcoids are fibroblastic skin tumours affecting equids worldwide. while the pathogenesis is not entirely understood, infection with bovine papillomavirus (bpv) type 1 (and less commonly type 2) has been implicated as a major factor in the disease process. sarcoids very seldom regress and in fact often recrudesce following therapy. nothing is known about the immune response of the equine host to bpv. given that the viral genes are expressed in sarcoids, it is reasonable to assume that vac ...200818089738
genomic and phylogenetic analysis of two novel bovine papillomaviruses, bpv-9 and bpv-10.eight bovine papillomavirus (bpv) types, bpv-1-8, have been classified, based on genome nucleotide sequence similarities, in the genera deltapapillomavirus (bpv-1 and -2), epsilonpapillomavirus (bpv-5 and -8), xipapillomavirus (bpv-3, -4 and -6) and an unassigned genus (bpv-7). we report here the complete genome sequence of two new bpv types isolated from separate epithelial squamous papilloma lesions on cattle teats. the genomes are 7,303 and 7,399 bp in length, respectively, and both have gene ...200818089739
high prevalence of bovine papillomaviral dna in the normal skin of equine sarcoid-affected and healthy horses.bovine papillomavirus (bpv), the causative agent of papillomas in cattle, has been shown to play a major role in the pathogenesis of equine sarcoids in horses. bpv has also been detected occasionally in normal equine skin. in this study, presence and activity of bpv in normal skin and peripheral blood of 4 groups of horses were evaluated: sarcoid-affected horses, horses living in contact with sarcoid-affected horses, horses living in contact with papilloma-affected cattle and control horses. fro ...200818093754
bovine papillomavirus type 4 l1 gene transfection in a drosophila s2 cell expression system: absence of l1 protein expression.the development of a bovine papillomavirus (bpv) vaccine is an outstanding challenge. bpv protein l1 gene transfection in the drosophila melanogaster s2 cell expression system failed to produce l1 protein notwithstanding correct l1 gene insertion. severe genetic inbalance in the host cell line, including cytogenetic alterations, may account for the lack of protein expression.200824031166
cuzn-sod suppresses the bovine papillomavirus-induced proliferation of fibroblasts.eukaryotic cells continuously produce reactive oxygen species (ros) and have mechanisms to control ros levels. ros have been shown to mediate cell proliferation and transformation. we studied the effect of cuzn-superoxide dismutase (cuznsod) on the focus-forming ability of bovine papillomavirus (bpv-1) wtdna and hypertransforming mutant of its major oncoprotein e5, e5-17s. we found that cuznsod suppresses the focus-forming ability of bpv-1 wtdna and e5 oncoprotein. significantly fewer foci were ...200718184412
nucleocytoplasmic shuttling of bovine papillomavirus e1 helicase downregulates viral dna replication in s phase.the papillomavirus e1 protein is essential for the initiation of viral replication. we previously showed that the bovine papillomavirus e1 protein is unstable and becomes resistant to ubiquitin-mediated degradation when tightly bound to cyclin e-cyclin-dependent kinase 2 (cdk2) before the start of dna synthesis. however, neither the protection nor the targeted degradation of e1 appears to depend on its phosphorylation by cdk. here, we report that cdk phosphorylation of e1 is also not a prerequis ...200717035309
vaccination with prion peptide-displaying papillomavirus-like particles induces autoantibodies to normal prion protein that interfere with pathologic prion protein production in infected cells.prion diseases are fatal neurodegenerative disorders caused by proteinaceous infectious pathogens termed prions (prp(sc)). to date, there is no prophylaxis or therapy available for these transmissible encephalopathies. passive immunization with monclonal antibodies recognizing the normal host-encoded prion protein (prp(c)) has been reported to abolish prp(sc) infectivity and to delay onset of disease. because of established immunologic tolerance against the widely expressed prp(c), active immuni ...200717313482
nuclear import of bovine papillomavirus type 1 e1 protein is mediated by multiple alpha importins and is negatively regulated by phosphorylation near a nuclear localization signal.papillomavirus dna replication occurs in the nucleus of infected cells and requires the viral e1 protein, which enters the nuclei of host epithelial cells and carries out enzymatic functions required for the initiation of viral dna replication. in this study, we investigated the pathway and regulation of the nuclear import of the e1 protein from bovine papillomavirus type 1 (bpv1). using an in vitro binding assay, we determined that the e1 protein interacted with importins alpha3, alpha4, and al ...200717192311
atp-dependent minor groove recognition of ta base pairs is required for template melting by the e1 initiator protein.template melting is an essential step in the initiation of dna replication, but the mechanism of template melting is unknown for any replicon. here we demonstrate that melting of the bovine papillomavirus type 1 ori is a sequence-dependent process which relies on specific recognition of ta base pairs in the minor groove by the e1 initiator. we show that correct template melting is a prerequisite for the formation of a stable double hexamer with helicase activity and that ori mutants that fail to ...200717202221
a papillomavirus-like particle (vlp) vaccine displaying hpv16 l2 epitopes induces cross-neutralizing antibodies to hpv11.peptides of the papillomavirus l2 minor capsid protein can induce antibodies (ab) that neutralize a broad range of human papillomavirus (hpv) genotypes. unfortunately, l2 is antigenically subdominant to l1 in the virus capsid. to induce a strong anti-l2 ab response with cross-neutralizing activity to other mucosal types, chimeric virus-like particles (vlp) were generated in which hpv16 l2 neutralization epitopes (comprising l2 residues 69-81 or 108-120) are inserted within an immunodominant surf ...200717239496
the crystal structure of the sv40 t-antigen origin binding domain in complex with dna.dna replication is initiated upon binding of "initiators" to origins of replication. in simian virus 40 (sv40), the core origin contains four pentanucleotide binding sites organized as pairs of inverted repeats. here we describe the crystal structures of the origin binding domain (obd) of the sv40 large t-antigen (t-ag) both with and without a subfragment of origin-containing dna. in the co-structure, two t-ag obds are oriented in a head-to-head fashion on the same face of the dna, and each t-ag ...200717253903
mva e2 recombinant vaccine in the treatment of human papillomavirus infection in men presenting intraurethral flat condyloma: a phase i/ii study.human papillomavirus (hpv) is the etiologic agent for warts and cervical cancer. in mexico, the death rate from cervical cancer is extremely high, and statistical data show that since 1990 the number of deaths is increasing. condylomas and cancer of the penis are the most common lesions presented in men; bladder and prostate cancer in men are also associated with the presence of hpv. since hpv is transmitted by sexual intercourse, treating both partners is necessary in order to eliminate the vir ...200717263589
complete genomes and phylogenetic positions of bovine papillomavirus type 8 and a variant type from a european bison.the dna of bovine papillomavirus (bpv) type 8 was extracted from papillomas on cattle kept in japan, and dna of bovine papillomavirus bpv-8-eb was extracted from a european bison (bison bonasus) born in italy and released into the wild in slovakia. the dna genomes of these bpvs were amplified using multiply primed rolling circle amplification and polymerase chain reaction, then characterized by direct sequencing method. the bpv-8 and bpv-8-eb genomes consisted of 7,791 base pairs (bp) and 7,773 ...200717265141
mitogen-activated protein kinases activate the nuclear localization sequence of human papillomavirus type 11 e1 dna helicase to promote efficient nuclear import.human and animal papillomavirus dna replicates as multicopy nuclear plasmids. replication requires two viral proteins, the origin-recognition protein e2 and the replicative dna helicase e1. using genetic, biochemical, and immunofluorescence assays, we demonstrated that efficient nuclear import of the human papillomavirus (hpv) type 11 e1 protein depends on a codominant bipartite nuclear localization sequence (nls) and on phosphorylation of the serine residues s89 and s93 by the mitogen-activated ...200717344281
the dna binding domain of a papillomavirus e2 protein programs a chimeric nuclease to cleave integrated human papillomavirus dna in hela cervical carcinoma cells.viral dna binding proteins that direct nucleases or other protein domains to viral dna in lytically or latently infected cells may provide a novel approach to modulate viral gene expression or replication. cervical carcinogenesis is initiated by high-risk human papillomavirus (hpv) infection, and viral dna persists in the cancer cells. to test whether a dna binding domain of a papillomavirus protein can direct a nuclease domain to cleave hpv dna in cervical cancer cells, we fused the dna binding ...200717392356
molecular dynamics of the dna-binding domain of the papillomavirus e2 transcriptional regulator uncover differential properties for dna target accommodation.papillomaviruses are small dna tumor viruses that infect mammalian hosts, with consequences from benign to cancerous lesions. the early protein 2 is the master regulator for the virus life cycle, participating in gene transcription, dna replication, and viral episome migration. all of these functions rely on primary target recognition by its dimeric dna-binding domain. in this work, we performed molecular dynamics simulations in order to gain insights into the structural dynamics of the dna-bind ...200717403036
identification and functional analysis of sequence variants in the long control region and the e2 open reading frame of bovine papillomavirus type 1 isolated from equine sarcoids.bpv-1 dna is the predominant viral type detected in equine sarcoids and represents the only reported natural cross species infection of papillomaviruses. in this study, nucleotide variations in the lcr and the e2 regions of equine sarcoid-associated bpv-1 were characterised by sequence analysis. variants particular to sarcoid bpv-1 were identified in both the lcr and e2 sequence. the functionality of the most common lcr variant was examined in equine and bovine cells. these studies showed that t ...200717412385
calcium enhances mouse keratinocyte differentiation in vitro to differentially regulate expression of papillomavirus authentic and codon modified l1 genes.here, we first wished to establish for mouse primary keratinocytes (kcs) the ca(2+) concentrations that were associated with kc differentiation in vitro. using the range of ca(2+) concentrations (0-6 mm) to differentiate primary kcs in culture to varying extents for 2 days, we then examined how kc differentiation impacted on expression of papillomavirus (pv) native (nat) and codon modified (mod) l1 genes. l1 mrnas transcribed from either nat or mod l1 genes were present in similar amounts in kcs ...200717462691
bovine papillomavirus type 1 infection is mediated by snare syntaxin 18.events that lead to viral infections include the binding of the virus to the target cells, internalization of the virus into the cells, and the ability of the viral genome to be expressed. these steps are mediated by cellular and viral proteins and are temporally regulated. the papillomavirus capsid consists of two virally encoded capsid proteins, l1 and l2. much is known about the role of the major capsid protein l1 compared to what is known of the role of the l2 protein. we identified the inte ...200717475643
transcription activator structure reveals redox control of a replication initiation reaction.redox changes are one of the factors that influence cell-cycle progression and that control the processes of cellular proliferation, differentiation, senescence and apoptosis. proteins regulated through redox-sensitive cysteines have been characterized but specific 'sulphydryl switches' in replication proteins remain to be identified. in bovine papillomavirus type-1, dna replication begins when the viral transcription factor e2 recruits the viral initiator protein e1 to the origin of dna replica ...200717478495
prophylactic dna immunization against multiple papillomavirus types.at least 15 different papillomavirus types are causatively associated with the development of tumors in humans. since the middle of 2006 a protective, virus-like particle based vaccine against the tumor-related hpv types 16 and 18 is commercially available. we investigated the possibility of applying dna vaccination to obtain protective antibody responses against multiple papillomavirus types. our data indicate that low amounts of dna were sufficient to induce neutralizing antibodies in mice alt ...200717485151
genital warts in burmeister's porpoises: characterization of phocoena spinipinnis papillomavirus type 1 (pspv-1) and evidence for a second, distantly related pspv.we identified sequences from two distantly related papillomaviruses in genital warts from two burmeister's porpoises, including a pv antigen-positive specimen, and characterized phocoena spinipinnis papillomavirus type 1 (pspv-1). the pspv-1 genome comprises 7879 nt and presents unusual features. it lacks an e7, an e8 and a bona fide e5 open reading frame (orf) and has a large e6 orf. pspv-1 l1 orf showed the highest percentage of nucleotide identity (54-55 %) with human papillomavirus type 5, b ...200717554024
complete genome and phylogenetic position of bovine papillomavirus type 7.six bovine papillomavirus (bpv) types and 16 putative bpv types have been reported previously. here, the complete genome sequence of bapv6, a novel putative bpv type isolated from cattle in japan, was determined by using multiple-primed rolling-circle amplification. the genome consisted of 7412 bp (g+c content of 46 mol%) that encoded five early (e1, e2, e4, e6 and e7) and two late (l1 and l2) genes, but did not encode the e5 gene. the e6 protein contained a non-consensus cxxc(x)(33)cxxc and a c ...200717554025
bovine papillomavirus e7 oncoprotein inhibits anoikis.the bovine papillomavirus type 1 (bpv-1) e7 oncoprotein is required for the full transformation activity of the virus. although bpv-1 e7 by itself is not sufficient to induce cellular transformation, it enhances the abilities of the other bpv-1 oncogenes to induce anchorage independence. we have been exploring the mechanisms by which e7 might affect the transformation efficiency of other viral oncoproteins and in particular whether it might protect cells from apoptosis. we report here that bpv-1 ...200717596310
packing contacts can mediate highly specific interactions between artificial transmembrane proteins and the pdgfbeta receptor.we used proteins with randomized transmembrane (tm) domains to explore the role of hydrophobic amino acids in mediating specific interactions between transmembrane helices. the 44-aa bovine papillomavirus e5 protein, which binds to the tm domain of the pdgfbeta receptor (pdgfbetar) was used as a scaffold to construct a library encoding small dimeric proteins with randomized, strictly hydrophobic tm domains, and proteins were selected that induced focus formation in mouse c127 cells by activating ...200717609376
generalized substitution of isoencoding codons shortens the duration of papillomavirus l1 protein expression in transiently gene-transfected keratinocytes due to cell differentiation.recently we reported that gene codon composition determines differentiation-dependent expression of the pv l1 genes in mouse primary keratinocytes (kcs) in vitro and in vivo (zhao et al. 2005, mol. cell biol. 25:8643-8655). here, we investigated whether generalized substitution of isoencoding codons affects the duration of expression of pv l1 genes in mouse and human kcs in day 1 culture transiently transfected with native (nat) and codon modified (mod) l1 genes. following transient transfection ...200717621583
bovine papillomavirus load and mrna expression, cell proliferation and p53 expression in four clinical types of equine sarcoid.equine sarcoids, the most common skin tumours in horses, are induced by bovine papillomavirus (bpv). their clinical appearance varies from small stable patches to aggressively growing masses. differences in bpv load and mrna expression and ki67 and p53 immunostaining among four clinical types (fibroblastic, occult, nodular and verrucous sarcoids) were evaluated to test the hypothesis that the clinical behaviour of equine sarcoids correlates with bpv activity. viral load and expression of the bpv ...200717622617
sialic acid and gm3 ganglioside expression in papillomavirus-associated urinary bladder tumours of cattle with chronic enzootic haematuria.this study was based on 30 papillomavirus-associated urinary bladder tumours from cattle with chronic haematuria, the animals having been kept since birth on pasture rich in bracken fern. the ganglioside content was assessed and compared with that of normal bovine urinary bladders, which was shown to be 28.6+/-3.3 (mean+/-sd) microg of lipid-bound sialic acid per gram of fresh tissue. in neoplastic bladder samples this value was higher but variable (120.9+/-80.6 in benign tumours, and 94.7+/-45. ...200717624364
brd4-independent transcriptional repression function of the papillomavirus e2 proteins.the papillomavirus e2 protein is a critical viral regulatory protein with transcription, dna replication, and genome maintenance functions. we have previously identified the cellular bromodomain protein brd4 as a major e2-interacting protein and established that it participates in tethering bovine papillomavirus type 1 e2 and viral genomes to host cell mitotic chromosomes. we have also shown that brd4 mediates e2-dependent transcriptional activation, which is strongly inhibited by the disruption ...200717626100
protection of rabbits against challenge with rabbit papillomaviruses by immunization with the n terminus of human papillomavirus type 16 minor capsid antigen l2.current l1 virus-like particle (vlp) vaccines provide type-restricted protection against a small subset of the human papillomavirus (hpv) genotypes associated with cervical cancer, necessitating continued cytologic screening of vaccinees. cervical cancer is most problematic in countries that lack the resources for screening or highly multivalent hpv vlp vaccines, suggesting the need for a low-cost, broadly protective vaccinogen. here, n-terminal l2 polypeptides comprising residues 1 to 88 or 11 ...200717715230
human papillomavirus e6 regulates the cytoskeleton dynamics of keratinocytes through targeted degradation of p53.the attachment and spreading of keratinocyte cells result from interactions between integrins and immobilized extracellular matrix molecules. human papillomavirus type 16 (hpv-16) e6 augmented the kinetics of cell spreading, while e6 genes from hpv-11 or bovine papillomavirus type 1 did not. the ability of e6 to interact with the e6ap ubiquitin ligase and target p53 degradation was required to augment cell-spreading kinetics; dominant negative p53 alleles also enhanced the kinetics of cell sprea ...200717804489
papillomavirus e1 helicase assembly maintains an asymmetric state in the absence of dna and nucleotide cofactors.concerted, stochastic and sequential mechanisms of action have been proposed for different hexameric aaa+ molecular motors. here we report the crystal structure of the e1 helicase from bovine papillomavirus, where asymmetric assembly is for the first time observed in the absence of nucleotide cofactors and dna. surprisingly, the atp-binding sites adopt specific conformations linked to positional changes in the dna-binding hairpins, which follow a wave-like trajectory, as observed previously in t ...200717881379
a protective and broadly cross-neutralizing epitope of human papillomavirus l2.we generated a monoclonal antibody, rg-1, that binds to highly conserved l2 residues 17 to 36 and neutralizes human papillomavirus 16 (hpv16) and hpv18. passive immunotherapy with rg-1 was protective in mice. antiserum to the hpv16 l2 peptide comprising residues 17 to 36 (peptide 17-36) neutralized pseudoviruses hpv5, hpv6, hpv16, hpv 18, hpv31, hpv 45, hpv 52, hpv 58, bovine papillomavirus 1, and hpv11 native virions. depletion of hpv16 l2 peptide 17-36-reactive antibodies from cross-neutralizi ...200717928339
differential expression of papillomavirus l1 proteins encoded by authentic and codon modified l1 genes in methylcellulose-treated mouse keratinocytes.papillomaviruses (pvs) are double-stranded dna viruses that infect keratinocytes in differentiating epithelia and induce hyperproliferative lesions. here, we used methylcellulose to induce cell differentiation of primary mouse keratinocytes (kcs) in in vitro culture and assessed the expression of authentic and codon-modified version of l1 capsid genes from two pv types (hpv6b and bpv1). based on the quantitative rt-pcr analysis, methylcellulose treatment did not influence the transcriptional exp ...200718036255
e6ap-dependent degradation of dlg4/psd95 by high-risk human papillomavirus type 18 e6 protein.in most cervical cancers, dnas of high-risk mucosotropic human papillomaviruses (hpvs), such as types 16 and 18, are maintained so as to express two viral proteins, e6 and e7, suggesting that they play important roles in carcinogenesis. the carboxy-terminal pdz domain-binding motif of the e6 proteins is in fact essential for transformation of rodent cells and induction of hyperplasia in e6-transgenic mouse skin. to date, seven pdz domain-containing proteins, including dlg1/hdlg, which is a human ...200717121805
bovine papillomavirus type-2 dna and expression of e5 and e7 oncoproteins in vascular tumours of the urinary bladder in cattle.cattles suffering from chronic enzootic haematuria frequently develop urinary bladder tumours of both epithelial and mesenchymal origin mainly haemangioma and its malignant counterpart. the role of the bovine papillomavirus type-2 (bpv-2) and of its major transforming oncoprotein in naturally occurring urothelial carcinogenesis has been recently clarified. e5 interacts in vivo as in vitro with the beta receptor for the platelet-derived growth factor (pdgf). however, studies regarding tumours of ...200717125915
genus specific features of bovine papillomavirus e6, e7, e5 and e8 proteins.six bovine papillomavirus (bpv) types, bpv-1 to -6, have been classified in genera delta-papillomavirus (bpv-1 and -2), epsilon-papillomavirus (bpv-5) and xi-papillomavirus (bpv-3, -4 and -6). in addition, 16 unclassified putative bpv types have been reported. in the present study, we characterized genus specific features of e6, e7, e5 (formerly e8) and e8 proteins of seven putative bpv types, bapv-1, -2, -3, -4 and -10, baa-5 and bpv-3c. these putative bpv types were classified in genera epsilo ...200717126443
mitotic kinesin-like protein 2 binds and colocalizes with papillomavirus e2 during mitosis.mklp2 is a kinesin-like motor protein of the central mitotic spindle required for completion of cytokinesis. papillomavirus e2 is a sequence specific dna binding protein that regulates viral transcription and replication and is responsible for partitioning viral episomes into daughter cells during cell division. we demonstrate that mklp2 specifically associates with the e2 protein during mitosis. using chromatin immunoprecipitation, we show viral genomes are in complex with mklp2 only within thi ...200717135315
detection of bovine papillomavirus type 1 genomes and viral gene expression in equine inflammatory skin conditions.papillomaviruses are normally strictly species-specific and even under experimental conditions do not usually infect any other host than the natural host. the only documented reports of natural papillomavirus cross-species infection are of bpv-1/bpv-2, which can infect horses and induce equine sarcoids. bpv dna has not been detected in non-sarcoid equine tumours or equine papillomas, but its presence has been reported in some cases of equine dermatitis. in the present study, we show that equine ...200717140693
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