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synergism between bovine papillomavirus type 4 and the flavonoid quercetin in cell transformation in vitro.bovine papillomavirus type 4 (bpv-4) morphologically transforms primary bovine cells in vitro only in the presence of an activated ras gene. the transformed cells are capable of anchorage-independent growth, but are not immortal and are incapable of inducing tumors in nude mice, suggesting that other events are needed to convert the cells to the fully transformed phenotype. we show here that treatment of the cells with a single dose of the flavonoid quercetin leads to full oncogenic transformati ...19921325710
phylogenetic analysis of 48 papillomavirus types and 28 subtypes and variants: a showcase for the molecular evolution of dna viruses.papillomaviruses are attractive models for studying the molecular evolution of dna viruses because of the large number of isolates that exhibit genomic diversity and host species and tissue specificity. to examine their relationship, we selected two amino acid sequences, one of 52 residues within the early gene e1 and the other of 44 residues within the late gene l1, which allowed insertion- and deletion-free alignment of all accessible papillomavirus sequences. we constructed phylogenetic trees ...19921326639
the b subgroup bovine papillomaviruses lack an identifiable e6 open reading frame.analysis of the corrected dna sequence for the bovine papillomavirus type 4 (bpv4) genome revealed that there is no open reading frame (orf) that might encode an e6 protein. the other two b subgroup bovine papillomaviruses, bpv3 and bpv6, were found to have the same arrangement of orfs in this region as bpv4. thus, we conclude that e6 functions are either not required by these viruses or are performed by another viral (or host) protein. furthermore, the position that might be expected to be occu ...19911654923
positive and negative e2-independent regulatory elements in the long control region of bovine papillomavirus type 4.the long control region (lcr) of bovine papilloma-virus type 4 demonstrated enhancer activity when cloned upstream of a bacterial chloramphenicol acetyltransferase reporter gene under thymidine kinase promoter control. deletion analysis of the lcr revealed the presence of several positive and negative control elements, all of which could function independently of the viral e2 trans-activator. each of the three positive elements present appeared to be paired with a negative element which modulate ...19911849970
malignant transformation of a papilloma induced by bovine papillomavirus type 4 in the nude mouse renal capsule.a papillomatous cyst was induced by implanting bovine foetal palate epithelium, infected in vitro with bovine papillomavirus type 4 (bpv-4), beneath the renal capsule of a nude mouse. the benign tumour underwent malignant progression, developing into a squamous cell carcinoma with metastatic deposits in the spleen. the bovine origin of both the renal and splenic cancers was confirmed by the presence of bovine major histocompatibility complex class i antigens in the cancer cells and by sequencing ...19911851817
studies on vaccination against papillomaviruses: the immunity after infection and vaccination with bovine papillomaviruses of different types.calves, free of antibodies to bovine papillomaviruses (bpv), were reared in isolation. one was infected with bpv-2, developed tumours and was resistant to homologous reinfection. groups of calves were infected with bpv-2, bpv-5 or bpv-6; they all developed and subsequently rejected type-specific tumours. they were then infected with bpv-4; they were not immune and oral papillomas were induced. groups of animals were vaccinated by intramuscular preparations of purified bpv-4 and bpv-6 and were ch ...19902161579
cooperation between bovine papillomavirus type 4 and ras in the morphological transformation of primary bovine fibroblasts.primary bovine fibroblasts derived from foetal palate can be transformed by bovine papillomavirus type 4 dna only in the presence of an activated ras gene, indicating that the virus does not encode all the information required for morphological transformation of non-established cells. a subgenomic fragment containing the complete e8 and e7 open reading frames (orfs) induces transformation in cooperation with activated ras but transformation is abolished when the e7 orf is deleted at the 3' end, ...19902177095
amplification of specific dna sequences in c127 mouse cells transformed by bovine papillomavirus type 4.a rearranged bovine papillomavirus type 4 dna fragment, present in a line of transformed c127 cells, was molecularly cloned into lambda gt 10. the rearranged viral fragment was found to consist of two separate sequences of 3.8 kb each. clone a comprised 3.3 kb of host dna linked to 0.5 kb of bpv-4 dna. clone b consisted of 2.2 kb of host dna linked to 1.5 kb of bpv-4 dna. the ab locus was found to be amplified and rearranged in a number of different bpv-4 transformed c127 cell lines, irrespectiv ...19892541389
induction of virus-producing tumours in athymic nude mice by bovine papillomavirus type 4.bovine papillomavirus type 4 (bpv-4), the causative agent of alimentary papillomatosis, has been used to infect, in vitro, fragments of palatine mucosa from late term bovine fetuses. these small explants were placed beneath the renal capsule of athymic nude mice where they grew to produce, at first, squamous epithelial cysts containing bpv-4 genomic dna and, later, papillomas which were morphologically identical to those of cattle and which contained large amounts of replicating virus. the possi ...19892554558
papillomas and cancer in cattle.papillomaviruses induce hyperproliferation of epithelial cells of the skin or mucosa (papillomas), and certain types can also infect fibroblasts. they are a very heterogeneous group of viruses, and individual types are associated with specific lesions. the papillomas are mostly benign but some tumours may eventually undergo malignant conversion when genetic or environmental factors are involved. in cattle, bovine papillomavirus type 4 (bpv-4) is the causative agent of papillomas of the alimentar ...19872825987
"hit and run" transformation of mouse c127 cells by bovine papillomavirus type 4: the viral dna is required for the initiation but not for maintenance of the transformed phenotype.morphological transformation of c127 mouse fibroblasts by bovine papillomavirus type 4 (bpv-4) dna depends on additional factors, including cell density, the presence of tpa, the concentration of fetal calf serum, and the physical state of the input dna. low cell density or the presence of tpa allows the achievement of full transformation, suggesting that disturbance of cell-to-cell contact may be necessary for the expression of the malignant phenotype. tpa also induces a burst of viral dna synt ...19882834874
mapping of two novel transcripts of bovine papillomavirus type 4.a cdna library was synthesized using rna from bovine papillomavirus type 4 (bpv-4)-induced papillomas. the major viral transcript was characterized by sequencing of its cdna, primer extension mapping and s1 nuclease protection studies. the transcript initiates at multiple sites between nucleotide (nt) 777 and nt 902, contains a splice junction between nt 1016 and nt 3376 and terminates at nt 4034, using the early polyadenylation signal at nt 4009. sequencing of viral cdnas and mrna revealed devi ...19882848926
r-loop mapping of rna transcripts from bovine papillomavirus type 4.rna isolated from bovine oesophageal warts was hybridised to bpv-4 genomic dna cloned in a plasmid vector. in r-loop preparations, six major classes of transcripts were mapped. class i, due to an unspliced transcript encompassing the e4/e5 orf region, is most common. in class ii the e4/e5 region is spliced at its 5' end to the e6 orf region, and the rnas appear to have different transcription start points in the e6 orf. some class i r-loops may represent shorter class ii-type transcripts not hyb ...19882855468
transcriptional organization of bovine papillomavirus type 4.seven virus-specific rna transcripts have been identified in tumours induced by bovine papillomavirus type 4 (bpv-4). the rnas measured 4.2, 3.6, 3.0, 2.8, 1.9, 1.6 and 1.0 kilobases (kb). they were mapped on the viral genome by northern blot hybridization to subgenomic probes, by cdna hybridization to viral dna fragments and by s1 analysis of unlabelled and 3' and 5' end-labelled dna fragments. all the rna species are transcribed from the same dna strand, are polyadenylated and with the excepti ...19862878058
the presence of bovine papillomavirus type 4 dna is not required for the progression to, or the maintenance of, the malignant state in cancers of the alimentary canal in cattle.in the western highlands of scotland there is a very high incidence of alimentary cancers in cattle. the carcinomas of the upper alimentary canal are found in association with virus-induced benign papillomas, and transformation of papillomas to carcinomas has been observed. strong circumstantial evidence suggests that the progression to malignancy is due to the interplay between the virus, bovine papillomavirus type 4 (bpv-4), and carcinogen(s) present in bracken fern, which infests the marginal ...19852992946
viral dna sequences detected in a hamster liposarcoma induced by bovine papillomavirus type 4.following intradermal inoculation of bovine papillomavirus type 4 (bpv-4) into a syrian hamster, a liposarcoma developed at the inoculation site 20 months later. the dna of this tumour contained multiple copies of the bpv-4 genome which existed in a free unintegrated state. unintegrated viral dna and viral dna isolated from virus particles from bovine alimentary tract papillomas revealed identical cleavage patterns with cpg methylation-resistant and -sensitive restriction enzymes: apparently the ...19863003234
papillomavirus infection in cattle: viral and chemical cofactors in naturally occurring and experimentally induced tumours.six different types of bovine papillomavirus (bpv-1 to bpv-6) have been identified and classified into two subgroups: subgroup a, which induce fibropapillomas, and subgroup b, which induce true epithelial papillomas. bpv-4, a member of subgroup b, is the aetiological agent of papillomas of the upper alimentary canal, which can become a focus for transformation to squamous-cell carcinomas in animals feeding on bracken fern. strong circumstantial evidence suggests that the progression to malignanc ...19863013519
the nucleotide sequence and genome organization of bovine papillomavirus type 4.the nucleotide sequence of bovine papillomavirus type 4 (bpv-4) was determined. the viral genome is 7261 base pairs long. several overlapping open reading frames (orfs) have been identified both on the basis of amino acid comparison with other papillomaviruses and on their transcriptional pattern. eight early orfs (e1 to 8) were recognized, coding for dna replication and cell transformation functions, and three late orfs (l1 to 3), coding for structural proteins. like the e5 orf of human papillo ...19873039043
papillomas of the teats and udder of cattle and their causal viruses.an abattoir survey was carried out on 1657 cattle to determine the incidence and parameters of teat and udder papillomas and their causal viruses. recent research has characterised six different bovine papillomaviruses of which three have been found to be particularly associated with teat tumours. of the population studied 37.3 per cent had teat warts and 86.2 per cent of these had multiple infections; 28.4 per cent had papillomas attributed to bovine papillomavirus 1, 88.5 per cent to bovine pa ...19846098066
molecular cloning of bovine papillomavirus genomes and comparison of their sequence homologies by heteroduplex mapping.the genomic dnas of bovine papillomavirus (bpv) type 1, type 2 and type 4 were cloned in pat153. bpv1 and bpv2 genomes were cloned using the single hindiii sites of the vector and virus dnas, and bpv4 was cloned using the single bamhi sites. the orientation of the recombinant dnas was established by restriction enzyme digestion, hybridization and heteroduplex analysis. the results showed that: (i) bpv1 and bpv2 dnas are in register and are broadly homologous throughout most of their length when ...19826296276
humoral immune response to the e7 protein of bovine papillomavirus type 4 and identification of b-cell epitopes.we have previously vaccinated cattle with e7, the major transforming protein of bovine papillomavirus-4, prior to homologous virus challenge. this retarded the development of papillomas and promoted their early regression compared to control animals. to understand the mechanism for this regression, we have studied the b and t cell response in vaccinated animals and compared it to that of non-vaccinated, virus-infected animals. the b cell response is reported here. the development of e7 igg antib ...19947510442
t cell responses to bpv-4 e7 during infection and mapping of t cell epitopes.vaccination of cattle with the recombinant e7 protein of bovine papillomavirus type 4 (bpv-4) prior to bpv-4 infection has been shown to retard development of papillomas and accelerate their regression. to understand the mechanism of regression we have measured proliferation of peripheral blood mononuclear cells (pbm) to e7 in vitro during the course of bpv-4 infection in both vaccinated and nonvaccinated cattle. in vaccinated cattle, t cells specific for e7 could be detected at high levels shor ...19957530395
vaccination of cattle with the n-terminus of l2 is necessary and sufficient for preventing infection by bovine papillomavirus-4.we have previously shown that cattle vaccinated with l2, the minor structural protein of bovine papillomavirus-4 (bpv-4), do not develop alimentary papillomas upon challenge with bpv-4. analysis of the b and t cell response in l2-vaccinated animals showed that the majority of the response was directed against the n-terminus and c-terminus of l2 with little response against the middle portion. cattle were vaccinated with the n-terminus or the c-terminus of l2. the animals vaccinated with the n-te ...19957544045
the synergism between bovine papillomavirus type 4 and quercetin is dependent on the timing of exposure.exposure to the flavonoid quercetin and transfection with bovine papillomavirus type 4 (bpv-4) dna lead to oncogenic transformation of primary bovine cells. here we show that the synergism between quercetin and bpv-4 (or its e7 oncogene) is stronger the shorter the interval between the two treatments. quercetin immortalizes transformed cells, confers anchorage-independent growth and induces tumorigenicity in cells transfected only with the e7 oncogene.19957634432
both viral e2 protein and the cellular factor pebp2 regulate transcription via e2 consensus sites within the bovine papillomavirus type 4 long control region.the bovine papillomavirus type 4 (bpv4) long control region (lcr) contains three consensus binding sites, e2(1), e2(2), and e2(3) (accn6ggt), for the viral e2 transcription factor and a fourth degenerate site, de2 (atcn6ggt), which lies 3 bp upstream of e2(3). the e2(2) site was found to bind the cellular transcription factor pebp2, and mutations at this site reduced basal promoter activity by as much as 60%, indicating an important role for pebp2 in lcr function. mutation of the e2(3) or de2 si ...19957666508
an element binding a c/ebp-related transcription factor contributes to negative regulation of the bovine papillomavirus type 4 long control region.deletion of the nr2 element of the long control region (lcr) of bovine papillomavirus type 4 (bpv-4) was observed previously to lead to a fivefold increase in enhancer activity of a subfragment of the lcr. further characterization of this element indicates that mutations in nr2 lead to increased enhancer activity in both mouse ct3 fibroblasts and in a transformed bovine epithelial cell line derived from an alimentary canal papilloma/in situ carcinoma, but not in primary bovine keratinocytes. sin ...19947964614
experimental reproduction of the papilloma-carcinoma complex of the alimentary canal in cattle.bovine papillomavirus type 4 (bpv-4) is the aetiological agent of epithelial papillomas of the upper alimentary canal in cattle. these benign tumours can become a focus for transformation to squamous cell carcinomas in animals feeding on bracken fern. strong epidemiological evidence suggests that the progression to malignancy is due to the interplay between bpv-4 and mutagenic and immunosuppressing chemicals present in the fern. the carcinomas of the upper alimentary canal are often accompanied ...19948055638
latent papillomavirus infection in cattle.during a long term experiment designed to identify the contribution of bovine papillomavirus type 4 (bpv-4), environmental mutagens and immunosuppressants to the development of carcinomas of the upper alimentary tract of cattle, there was evidence of latent papillomavirus infection. papillomatosis-free animals, when immunosuppressed either by feeding bracken fern or by azathioprine treatment, developed skin warts containing either bpv-1 or bpv-2. skin warts appeared also in an immunocompetent an ...19948191003
analysis of the transforming functions of bovine papillomavirus type 4.bovine papillomavirus type 4 (bpv-4) morphologically transforms primary bovine cells in vitro only in the presence of an activated ras gene. the transformed cells are capable of anchorage-independent growth, but are not immortal and are incapable of inducing tumors in nude mice. bpv-4 does not possess an e6 orf and failure to induce full transformation may be due to the lack of this gene. here we report the contribution of individual bpv-4 genes to cell transformation and the effect of adding th ...19938384749
prophylactic and therapeutic vaccination against a mucosal papillomavirus.papillomaviruses are ubiquitous dna viruses affecting humans and animals and causing a variety of tumours of mucosal and cutaneous epithelia. some of these lesions, particularly those affecting mucosal epithelia, can progress to squamous cell carcinomas. prevention or cure of viral infection would ultimately lead to a decrease in the incidence of papillomavirus-associated cancers. using recombinant proteins, we have developed prophylactic and therapeutic vaccines against bovine papillomavirus ty ...19938389809
interaction between bovine papillomavirus type 4 and cocarcinogens in the production of malignant tumours.bovine fetal palatine tissue infected with bovine papillomavirus type 4 (bpv-4) was implanted subcutaneously in athymic nude mice. the implants developed into cysts containing papillomas essentially the same as those in the natural host. in order to investigate the interaction of cocarcinogens with bpv-4 in cell transformation, the virus-infected implants were exposed in vivo to either the tumour promoter 12-o-tetradecanoylphorbol-13-acetate (tpa) or the tumour initiator 7,12-dimethylbenz[a]-ant ...19938409951
bovine papillomavirus type 4 in australia. 19958534233
virus-like particles of bovine papillomavirus type 4 in prophylactic and therapeutic immunization.virus-like particles were produced in insect cells containing either the l1 and l2 capsid proteins of bovine papillomavirus type 4 (bpv-4) or only the l1 protein. both preparations of vlps proved to be extremely effective prophylactic vaccines. thirteen of 15 calves immunised with either l1-l2 vlps or l1-vlps were refractory to experimental challenge with high doses of bpv-4 and did not develop papillomas, while 9 of 10 control animals developed multiple oral papillomas. vlps were not efficient ...19968623552
bovine papillomavirus type 4 dna isolated from a skin lesion in a steer.a lesion on the head of a steer, defined histologically as an epithelial papilloma, yielded dna which did not hybridise with any of the bovine papillomavirus dnas usually associated with the formation of skin lesions. dna from the lesion did hybridise with dna from bovine papillomavirus 4, even under stringent conditions, and contained a sequence that could be amplified by polymerase chain reaction with primers specific for that virus. bovine papillomavirus 4 had previously been isolated only fr ...19968733180
vaccination of cattle with bovine papillomavirus type 4 l2 elicits the production of virus-neutralizing antibodies.prophylactic vaccination of cattle with the n terminus (l2a, aa 11-200) of the minor capsid protein l2 completely prevented bovine papillomavirus type 4 (bpv-4) infection of the alimentary canal. to investigate the mechanisms underlying protection from viral infection, sera from vaccinated animals were analysed in neutralization assays both in the nude mouse xenograft system and in cattle. bpv-4 retained its infectivity when incubated with preimmune cattle sera, whereas, when incubated with immu ...19968758002
phenotypical characterization of lymphocytes infiltrating regressing papillomas.papillomavirus-induced lesions often regress spontaneously in both humans and animals. papilloma regression is deemed to be due to a cell-mediated immune response, the nature of which is still ill defined, and is accompanied by immune cell infiltrates. to gain further information on the nature and role of the immune cells present in regressing papillomas, we have analyzed biopsies of papillomas induced in the soft palate of cattle by bovine papillomavirus type 4 (bpv-4) and have phenotypically c ...19968970967
the bovine papillomavirus type 4 e8 protein binds to ductin and causes loss of gap junctional intercellular communication in primary fibroblasts.the e8 open reading frame of bovine papillomavirus type 4 encodes a small hydrophobic polypeptide which contributes to cell transformation by conferring anchorage-independent growth. using an in vitro translation system, we show that the e8 polypeptide binds to ductin, the 16-kda proteolipid that forms transmembrane channels in both gap junctions and vacuolar h+-atpase. this association is not due to nonspecific hydrophobic interactions. ppa1, a saccharomyces cerevisiae polypeptide homologous (w ...19968971040
viral proteins of bovine papillomavirus type 4 during the development of alimentary canal tumours.in cattle infection of the upper alimentary canal mucosa by bovine papillomavirus type 4 (bpv-4) results in the development of papillomas which can progress to cancer in animals fed on bracken fern. this paper describes a study of the cellular and subcellular distribution of a number of different bpv-4 products in experimentally-induced bpv-4 tumours. e8 and e4 proteins were detected solely as cytoplasmic antigens in the undifferentiated and differentiated layers of the papilloma, respectively; ...19979265855
a peptide encoding a b-cell epitope from the n-terminus of the capsid protein l2 of bovine papillomavirus-4 prevents disease.the first 200 n-terminus amino acids of the l2 capsid protein of bpv-4 (designated l2a) are an effective prophylactic vaccine against bpv-4 infection. vaccination with l2a induces the production of virus neutralizing antibodies, and when l2a antibodies are removed from immune sera, the sera lose their neutralization activity. l2a encodes three dominant b-cell epitopes, defined as epitope 1 (amino acids 101-120), epitope 2 (aa 131-151), and epitope 3 (aa 151-170). to investigate whether any of th ...19979268157
linear b-cell epitopes in the n-terminus of l2 of bovine papillomavirus type 4.the minor capsid protein l2 of bovine papillomavirus type 4 (bpv-4) is a very effective prophylactic vaccine which induces the production of virus neutralising antibodies and prevents virus-induced papillomatosis. the virus neutralising activity resides in the first 200 n-terminal amino acids of l2 (l2a). to further investigate the humoral immune response to l2, and the role it plays during infection and in prophylactic vaccination, the presentation of b-cell linear epitopes of l2a has been anal ...19979300551
the role of exogenous p53 and e6 oncoproteins in in vitro transformation by bovine papillomavirus type 4 (bpv-4): significance of the absence of an e6 orf in the bpv-4 genome.bovine papillomavirus type 4 (bpv-4) does not possess an e6 orf. the e6 oncoprotein of human papillomavirus (hpv) binds and degrades the tumour suppressor protein p53, thus contributing to tumour progression. since bpv-4 lacks e6, it is unknown how the virus evades the tumour suppressor properties of p53 in the induction of tumours of the gastrointestinal tract. mutations in the p53 gene have been detected both in papillomas and carcinomas, suggesting that p53 dysfunction plays a part in these n ...19979367387
bovine papillomavirus and cancer.bovine papillomavirus (bpv) induces papillomas of cutaneous or mucosal epithelia in cattle. the papillomas are benign tumours and generally regress, but occasionally persist and provide the focus for malignant transformation to squamous cell carcinoma, particularly in the presence of environmental cofactors. this has been experimentally demonstrated for bpv-2 and cancer of the urinary bladder, and bpv-4 and cancer of the upper alimentary canal in cattle feeding on bracken fern. in this review, s ...19979414951
epithelial specific transcriptional regulation of the bovine papillomavirus 4 promoter by e2.bovine papillomavirus 4 (bpv-4) is a mucosal epitheliotropic papillomavirus. it encodes a transcriptional regulator, e2, which acts on the bpv-4 transcriptional control region (the long control region or lcr) to regulate transcription. the distribution of e2 binding sites within the lcr of bpv-4 is identical to that of the human papillomaviruses hpv-16 and hpv-18, indicating that the mechanism of transcriptional control by e2 of mucosal epitheliotropic papillomaviruses is conserved. in this stud ...19989519828
bpv-4 e8 transforms nih3t3 cells, up-regulates cyclin a and cyclin a-associated kinase activity and de-regulates expression of the cdk inhibitor p27kip1.the e8 open reading frame of bovine papillomavirus type 4 (bpv-4) encodes a small (42 amino acid) hydrophobic polypeptide localized to cellular membranes and capable of conferring an anchorage-independent (ai) growth phenotype on primary bovine cells co-transfected with bpv-4 e7 orf and an activated ras gene. to further study the function of e8 independently of other viral gene products, we have expressed it in the murine fibroblast cell line, nih3t3. cells expressing e8 are capable of ai growth ...19989690511
the bovine papillomavirus type 4 long control region contains an epithelial specific enhancer.bovine papillomavirus type 4 (bpv-4) is a mucosal epitheliotropic virus that is a causative agent in alimentary carcinoma of cattle. the long control region (lcr) of this virus controls expression of the transforming proteins, e8 and e7. deletion mutants of the lcr were prepared and assayed for their ability to activate transcription from the lcr promoter in primary bovine palate keratinocytes (the natural target cell for bpv-4) and fibroblasts. the lcr was at least an order of magnitude more ac ...19999934679
a mutational analysis of the transforming functions of the e8 protein of bovine papillomavirus type 4.the e8 protein of bpv-4 contributes to transformation of primary bovine cells (palfs) by inducing anchorage-independent growth and by down-regulating gap junction intercellular communication, likely due to its binding to 16k ductin. we show here that, in addition, e8 confers on palf cells the ability to grow in low serum and to escape from contact inhibition (focus formation). e8 also transactivates an exogenous human cyclin a gene promoter, suggesting that overexpression of cyclin a is responsi ...199910069964
many different papillomaviruses have low transcriptional activity in spite of strong epithelial specific enhancers.transcription of the e6-e7 genes of human papillomavirus type 11 (hpv-11), hpv-16 and hpv-18 is specific to epithelial cells. this mechanism originates from synergism between different transcription factors such as ap-1, nfi and sp1, which occur in many different cell types, but whose activity is biased in favour of epithelial cells. in this study, the transcriptional regulation of 14 different papillomavirus types in the absence of the viral e2 transcription factor was compared. genital hpv typ ...199910423140
an enhanced epithelial response of a papillomavirus promoter to transcriptional activators.mucosal epitheliotropic papillomaviruses have a similar long control region (lcr) organization: a promoter region, an enhancer region, and a highly conserved distribution of e2 dna binding sites. the enhancer of these viruses is epithelial-specific, as it fails to activate transcription from heterologous promoters in nonepithelial cell types (gloss, b., bernard, h. u., seedorf, k., and klock, g. (1987) embo j. 6, 3735-3743; morgan, i. m., grindlay, g. j., and campo, m. s. (1999) j. gen. virol. 8 ...199910488130
alpha6 integrin is not the obligatory cell receptor for bovine papillomavirus type 4.recently, alpha6 integrin has been proposed as the epithelial cell receptor for papillomavirus. this study investigated whether alpha6 integrin is the cellular receptor for bovine papillomavirus type 4 (bpv-4), which is strictly epitheliotropic and infects the mucous epithelium of the upper digestive tract. primary bovine mucosal keratinocytes from the palate of a foetus (palk) displayed high levels of alpha6 integrin; matched primary fibroblasts from the same biopsy (palf) expressed almost no a ...200010644830
binding of bovine papillomavirus type 4 e8 to ductin (16k proteolipid), down-regulation of gap junction intercellular communication and full cell transformation are independent events.the e8 open reading frame of bovine papillomavirus type 4 encodes a small hydrophobic polypeptide that contributes to primary cell transformation by conferring to cells the ability to form foci and to grow in low serum and in suspension. wild-type e8 binds in vitro to ductin, a component of gap junctions, and this binding is accompanied by a loss of gap junction intercellular communication in transformed bovine fibroblasts. however, through the analysis of a panel of e8 mutants, we show here tha ...200010675405
alpha6 integrin is not the obligatory cell receptor for bovine papillomavirus type 4 200010811948
a novel silencer element in the bovine papillomavirus type 4 promoter represses the transcriptional response to papillomavirus e2 protein.the long control regions (lcrs) of mucosal epitheliotropic papillomaviruses have similar organizations: a promoter region, an enhancer region, and a highly conserved distribution of e2 dna binding sites (c. desaintes and c. demeret, semin. cancer biol. 7:339--347, 1996). the enhancer of these viruses is epithelial cell specific, as it fails to activate transcription from heterologous promoters in nonepithelial cell types (b. gloss, h. u. bernard, k. seedorf, and g. klock, embo j. 6:3735--3743, 1 ...200111222708
quercetin, e7 and p53 in papillomavirus oncogenic cell transformation.bovine papillomavirus type 4 (bpv-4) infects the upper alimentary canal of cattle causing benign papillomas which can progress to squamous carcinomas in cattle grazing on bracken fern (bf). we have previously shown that quercetin, a well characterized and potent mutagen found in bf, causes cell cycle arrest of primary bovine cells (palf), but that a single exposure to quercetin can cause full oncogenic transformation of palf cells partially transformed by bpv-4. here we show that cell cycle arre ...200111408351
cell transformation by the e5/e8 protein of bovine papillomavirus type 4. p27(kip1), elevated through increased protein synthesis is sequestered by cyclin d1-cdk4 complexes.the e5/e8 hydrophobic protein of bpv-4 is, at only 42 residues, the smallest transforming protein identified to date. transformation of nih-3t3 cells by e5/e8 correlates with up-regulation of both cyclin a-associated kinase activity and, unusually, p27(kip1) (p27) but does not rely on changes in cyclin e or cyclin e-cdk2 activity. here we have examined how p27 is prevented from functioning efficiently as a cdk2 inhibitor, and we investigated the mechanisms used to achieve elevated p27 expression ...200111448948
e5 transforming proteins of papillomaviruses do not disturb the activity of the vacuolar h(+)-atpase.papillomaviruses contain a gene, e5, that encodes a short hydrophobic polypeptide that has transforming activity. e5 proteins bind to the 16 kda subunit c (proteolipid) of the eukaryotic vacuolar h(+)-atpase (v-atpase) and this binding is thought to disturb the v-atpase and to be part of transformation. this link has been examined in the yeast saccharomyces cerevisiae. the e5 proteins from human papillomavirus (hpv) type 16, bovine papillomavirus (bpv) type 1, bpv-4 e5 and various mutants of e5 ...200111562529
bovine papillomavirus type 4 in oesophageal papillomas of cattle from the south of italy.oesophageal papillomas are known to occur in cattle infected with bovine papillomavirus type 4 (bpv-4), and bpv-4 papillomas may undergo malignant progression in cattle that feed on bracken fern. in the south of italy, where bracken fern is common, examination of 1133 slaughterhouse cattle aged 4-12 years revealed oesophageal lesions (single or multiple peduncuolated proliferations, or mucosal thickening) in 147 (13%). these two types of lesion were consistent with exophytic and inverted papillo ...200312634101
extensive papillomatosis of the bovine upper gastrointestinal tract.extensive papillomatosis was identified in a heifer born and raised in scotland and a steer born and raised in england. in both cases, the papillomas extended from the mouth and tongue to the reticulum. although cases of florid papillomatosis of the upper gastrointestinal tract occur relatively frequently in cattle grazing on bracken fern in the scottish highlands, no such cases have been reported previously in english cattle. histopathological examination of the papillomas showed that the lesio ...200312921714
quercetin elevates p27(kip1) and arrests both primary and hpv16 e6/e7 transformed human keratinocytes in g1.our previous work with primary bovine fibroblasts demonstrated that quercetin, a potent mutagen found in high levels in bracken fern (pteridium aquilinum), arrested cells in g1 and g2/m, in correlation with p53 activation. the expression of bovine papillomavirus type 4 (bpv-4) e7 overcame this arrest and lead to the development of tumorigenic cells lines (beniston et al., 2001). given the possible link between papillomavirus infection, bracken fern in the diet and cancer of the upper gastrointes ...200312934110
cyclin a expression and growth in suspension can be uncoupled from p27 deregulation and extracellular signal-regulated kinase activity in cells transformed by bovine papillomavirus type 4 e5.as the biochemical detection of bovine papillomavirus type 4 e5 is problematic, a fusion form of e5 and the green fluorescent protein (gfp-e5) was constructed and its characteristics were examined. gfp-e5 was detected in cells by autofluorescence and immunoblotting. like wild-type (wt) e5, gfp-e5 localized in the endomembranes and permitted anchorage-independent (ai) growth. however, unlike wt e5, cells expressing gfp-e5 became quiescent in low serum and failed to sustain expression of cyclins d ...200415557231
transactivation of the cyclin a promoter by bovine papillomavirus type 4 e5 protein.bovine papillomavirus type 4 (bpv-4) e5 (formerly e8) is a 42-residue hydrophobic, membrane-localised protein that can transform nih-3t3 cells by a poorly defined mechanism. in e5-expressing cells, the observed up-regulation of cyclin a is underpinned by transactivation of the cyclin a promoter. here we show that e5 transactivates the minimal cell cycle-regulated cyclin a promoter in cells both stably and acutely expressing the viral protein. there are no detectable differences between control a ...200515681052
hpv-18 transformed cells fail to arrest in g1 in response to quercetin treatment.previous work with primary human keratinocytes demonstrated that quercetin, a potent mutagen found in high levels in bracken fern (pteridium aquilinum), arrested cells in g1 with concomitant elevation of the cyclin-dependent kinase inhibitor (cdki) p27kip1. expression of the human papillomavirus type 16 (hpv-16) e6 and e7 oncoproteins, under transcriptional control of a heterologous promoter, in transformed keratinocytes failed to abrogate this arrest [beniston, r., campo, m.s., 2003. quercetin ...200515763151
dynamic localization of the human papillomavirus type 11 origin binding protein e2 through mitosis while in association with the spindle apparatus.papillomaviral dna replicates as extrachromosomal plasmids in squamous epithelium. viral dna must segregate equitably into daughter cells to persist in dividing basal/parabasal cells. we have previously reported that the viral origin binding protein e2 of human papillomavirus types 11 (hpv-11), 16, and 18 colocalized with the mitotic spindles. in this study, we show the localization of the hpv-11 e2 protein to be dynamic. it colocalized with the mitotic spindles during prophase and metaphase. at ...200616641272
down-regulation of mhc class i is a property common to papillomavirus e5 proteins.the e5 protein family of papillomaviruses comprises small hydrophobic proteins which are associated with the cell endomembrane compartments. the functions of the e5 proteins, particularly those of hpv, are still far from clear. we have reported that the e5 proteins of bpv-1, bpv-4, hpv-16 and hpv-6 down-regulate mhc class i, potentially helping the virus evade the host immune response. others have described mhc class i down-regulation by hpv-2 e5. we report here that another e5 protein, hpv-83 e ...200616780984
quercetin induces structural chromosomal aberrations and uncommon rearrangements in bovine cells transformed by the e7 protein of bovine papillomavirus type 4.bovine papillomavirus type 4 (bpv-4) and bracken fern are cofactors in the carcinogenesis of the upper gastrointestinal (gi) tract of cattle. an experimental in vitro model system has been developed to analyse the co-operation between the viral transforming protein e7, the cellular ras oncogene and quercetin, one of the mutagens of bracken fern, during neoplastic progression of primary bovine cells. we now report cytogenetic studies of these cells at different stages of malignant transformation: ...200319379326
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
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
bovine papillomavirus type 4.papillomavirus induce benign tumours (papillomas) in a variety of animals. the papillomas generally regress but occassionally persist and may eventually progress to squamous cell carcinoma. one of the most extensively studies papillomaviruses is bovine papillomavirus type 4 (bpv4). bpv-4 induces papillomas of the upper alimentary canal which are at high risk of progressing to cancer in cattle eating bracken fern. in this review, several aspects of the biology of the virus are described and compa ...199621541627
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
bos taurus papillomavirus activity in peripheral blood mononuclear cells: demonstrating a productive infection.bovine papillomavirus (bpv) is an oncogenic virus with mucous and epithelial tropism. possible productive virus infection in other tissues, such as blood, has been hypothesized. in order to investigate this possibility, three samples of skin papillomas and blood were collected from bovines with bpv infection and five samples of peripheral blood and one sample of normal tissue were collected from a calf without bpv infection. peripheral blood mononuclear cells (pbmcs) were isolated from whole blo ...201526681018
bovine papillomavirus in beef cattle: first description of bpv-12 and putative type bapv8 in brazil.bovine papillomavirus (bpv) is an oncogenic virus associated with benign and malignant lesions, which result in notable economic losses. peripheral blood samples and cutaneous papillomas were obtained from four adult beef cattle. viral molecular identification was performed using specific primers for bpv-1, -2 and -4 in blood diagnosis and fap59/fap64 for skin papillomas. histopathologic examination was done as a complementary and differential diagnosis. the fragments were purified, sequenced, a ...201425117322
expression of the bovine papillomavirus type 1, 2 and 4 l1 genes in the yeast pichia pastoris.papillomaviruses are known to cause benign or malignant lesions in various animals. in cattle, bovine papillomavirus (bpv) is the etiologic agent of papillomatosis and neoplasia of the upper gastrointestinal tract and urinary bladder. currently, there are no standard diagnostic tests or prophylactic vaccines. protection against papillomavirus infection is conferred by neutralizing antibodies directed towards the major structural protein l1. these antibodies can be efficiently induced by immuniza ...201222869085
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
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