papillomaviruses: progress for human and veterinary medicine. 19979414949
the papillomavirus minor capsid protein, l2, induces localization of the major capsid protein, l1, and the viral transcription/replication protein, e2, to pml oncogenic domains.we have used immunofluorescent staining and confocal microscopy to examine the subcellular localization of structural and nonstructural bovine papillomavirus (bpv) proteins in cultured cells that produce infectious virions. when expressed separately, l1, the major capsid protein, showed a diffuse nuclear distribution while l2, the minor capsid protein, was found to localize to punctate nuclear regions identified as promonocytic leukemia protein (pml) oncogenic domains (pods). coexpression of l1 ...19989420209
interaction of the bovine papillomavirus e6 protein with the clathrin adaptor complex ap-1.the e6 gene of the bovine papillomavirus type 1 (bpv-1) is expressed in fibropapillomas caused by bpv-1 and in tissue culture cells transformed by bpv-1. it encodes one of the two major oncoproteins of bpv-1. in this study, we demonstrate an interaction between the bpv-1 e6 protein and ap-1, the tgn (trans-golgi network)-specific clathrin adaptor complex. ap-1 is a four-subunit protein complex required for clathrin-mediated cellular transport from the tgn. the ap-1/e6 interaction was observed in ...19989420248
transient viral dna replication and repression of viral transcription are supported by the c-terminal domain of the bovine papillomavirus type 1 e1 protein.the bovine papillomavirus type 1 e1 protein is important for viral dna replication and transcriptional repression. it has been proposed that the full-length e1 protein consists of a small n-terminal and a larger c-terminal domain. in this study, it is shown that an e1 polypeptide containing residues 132 to 605 (which represents the c-terminal domain) is able to support transient viral dna replication, although at a level lower than that supported by the wild-type protein. this domain can also re ...19989420289
functional interaction of the bovine papillomavirus e2 transactivation domain with tfiib.induction of gene expression by the papillomavirus e2 protein requires its approximately 220-amino-acid amino-terminal transactivation domain (tad) to interact with cellular factors that lead to formation of an activated rna polymerase complex. these interaction partners have yet to be identified and characterized. the e2 protein localizes the transcription complex to the target promoter through its carboxy-terminal sequence-specific dna binding domain. this domain has been reported to bind the ...19989444994
polyomavirus large t can support dna replication in human cells.human cells are generally thought to be nonpermissive for polyomavirus (py) dna replication. using transient transfection, we show that py large t-antigen (lt) was able to support replication of a py origin-containing plasmid in two human cell lines. replication supported by lt in human cells was specific for the py origin and required its enhancer sequences, as well as the previously reported critical phosphorylation sites within lt. py replication efficiency was comparable to that of papilloma ...19989448688
papillomavirus virus-like particles can deliver defined ctl epitopes to the mhc class i evaluate an antigen delivery system in which exogenous antigen can target the major histocompatibility complex (mhc) class i pathway, a single human papillomavirus (hpv) 16 e7 cytotoxic t lymphocyte (ctl) epitope and a single hiv gp160 ctl epitope were separately fused to the c-terminus of bovine papillomavirus 1 (bpv1) l1 sequence to form hybrid bpv1l1 vlps. mice immunized with these hybrid vlps mounted strong ctl responses against the relevant target cells in the absence of any adjuvants. i ...19989448699
association of bovine papillomavirus type 1 e6 oncoprotein with the focal adhesion protein paxillin through a conserved protein interaction motif.we have found that the e6 oncoprotein of bovine papillomavirus type 1 (be6) as well as the e6 protein of the cancer associated hpv-16 (16e6) interact with the focal adhesion protein paxillin. mutational analysis of paxillin revealed that be6 binds paxillin through small protein interaction motifs called ld motifs that have been previously identified as important in regulating association of paxillin with vinculin and focal adhesion kinase (fak), and that be6 can interact with at least two separa ...19989467941
screening for bovine papillomavirus in peripheral blood cells of donkeys with and without sarcoids.papillomaviral dna has been identified in peripheral blood cells of both cattle and humans with and without associated disease and it has been suggested that such cells may act as sites of viral latency. in order to investigate the possibility of latent papillomaviral infection in the aetiopathogenesis of the equine sarcoid, peripheral blood derived dna samples from 20 healthy and 34 sarcoid-affected donkeys were subject to polymerase chain reaction (pcr) using papillomaviral specific primers. a ...19979491459
intercapsomeric disulfide bonds in papillomavirus assembly and order to analyze bonding contacts that stabilize the virion or promote capsid assembly, bovine papillomavirus (bpv) virions were subjected to buffer conditions known to disrupt polyomavirus virions. at physiologic ionic strength, incubation with dithiothreitol (dtt), egta, or dtt plus egta did not disrupt bpv virions as determined by electron microscopy. however, incubation of virions with dtt rendered the bpv l1 protein susceptible to trypsin cleavage at its carboxy terminus and rendered the ...19989499072
competition for dna binding sites between the short and long forms of e2 dimers underlies repression in bovine papillomavirus type 1 dna replication control.papillomaviruses establish a long-term latency in vivo by maintaining their genomes as nuclear plasmids in proliferating cells. bovine papillomavirus type 1 encodes two proteins required for viral dna replication: the helicase e1 and the positive regulator e2. the homodimeric e2 is known to cooperatively bind to dna with e1 to form a preinitiation complex at the origin of dna replication. the virus also codes for two short forms of e2 that can repress viral functions when overexpressed, and at l ...19989499046
bovine papillomavirus type 1 genomes and the e2 transactivator protein are closely associated with mitotic chromatin.the bovine papillomavirus type 1 e2 transactivator protein is required for viral transcriptional regulation and dna replication and may be important for long-term episomal maintenance of viral genomes within replicating cells (m. piirsoo, e. ustav, t. mandel, a. stenlund, and m. ustav, embo j. 15:1-11, 1996). we have evidence that, in contrast to most other transcriptional transactivators, the e2 transactivator protein is associated with mitotic chromosomes in dividing cells. the shorter e2-tr a ...19989499063
an embryonic demethylation mechanism involving binding of transcription factors to replicating vertebrates, transcriptionally active promoters are undermethylated. since the transcription factor sp1, and more recently nf-kappab, have been implicated in the demethylation process, we examined the effect of transcription factors on demethylation by injecting in vitro methylated plasmid dna into xenopus fertilized eggs. we found that various transactivation domains, including a strong acidic activation domain from the viral protein vp16, can enhance demethylation of a promoter region when ...19989482741
dna structure and flexibility in the sequence-specific binding of papillomavirus e2 proteins.the papillomavirus e2 proteins are transcriptional regulators that bind to a consensus dna sequence accg nnnn cggt. multiple copies of this binding site are found in the viral genomes. the affinities of the naturally occurring binding sites for the e2 proteins are predominantly dependent upon the sequence of the nnnn spacer. the hierarchies of binding site affinities among the sites present in the viral genomes result in differential occupancy during the viral life-cycle. in turn, this different ...19989500925
subunit rearrangement accompanies sequence-specific dna binding by the bovine papillomavirus-1 e2 protein.the 2.5 a crystal structures of the dna-binding domain of the e2 protein from bovine papillomavirus strain 1 and its complex with dna are presented. e2 is a transcriptional regulatory protein that is also involved in viral dna replication. it is the structural prototype for a novel class of dna-binding proteins: dimeric beta-barrels with surface alpha-helices that serve as recognition helices. these helices contain the amino-acid residues involved in sequence-specifying interactions. the e2 prot ...19989500927
the human papillomavirus type 18 (hpv18) replication protein e1 is a transcriptional activator when interacting with hpv18 e2.the human papillomavirus type 18 e1 and e2 proteins are both required for the initiation of viral dna replication. whereas e2 is the major viral transcription regulator, e1 is the replication initiator protein. they interact with each other and with the origin sequences to initiate viral dna replication. we show that the hpv18 e1 and e2 proteins, when bound to an origin sequence cloned upstream of a heterologous promoter, synergistically activate transcription. this synergy required binding of e ...19989514974
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
characterization of the dna-binding domain of the bovine papillomavirus replication initiator e1.the bovine papillomavirus replication initiator protein e1 is an origin of replication (ori)-binding protein absolutely required for viral dna replication. in the presence of the viral transcription factor e2, e1 binds to the ori and initiates dna replication. to understand how the e1 initiator recognizes the ori and how e2 assists in this process, we have expressed and purified a 166-amino-acid fragment which corresponds to the minimal e1 dna-binding domain (dbd). dna binding studies using this ...19989525573
stability without a centromere. 19989539691
segregation of viral plasmids depends on tethering to chromosomes and is regulated by phosphorylation.eukaryotic viruses can maintain latency in dividing cells as extrachromosomal nuclear plasmids. segregation and nuclear retention of dna is, therefore, a key issue in retaining copy number. the e2 enhancer protein of the papillomaviruses is required for viral dna replication and transcription. viral mutants that prevent phosphorylation of the bovine papillomavirus type 1 (bpv) e2 protein are transformation-defective, despite normal viral gene expression and replication function. cell colonies ha ...19989539738
transactivation-competent bovine papillomavirus e2 protein is specifically required for efficient repression of human papillomavirus oncogene expression and for acute growth inhibition of cervical carcinoma cell lines.the papillomavirus e2 proteins can function as sequence-specific transactivators or transrepressors of transcription and as cofactors in viral dna replication. we previously demonstrated that acute expression of the bovine papillomavirus type 1 (bpv1) e2 protein in hela and ht-3 cervical carcinoma cell lines greatly reduced cellular proliferation by imposing a specific g1/s phase growth arrest. in this report, we analyzed the effects of a panel of point mutations in the bpv1 e2 protein to identi ...19989557678
dna packaging by l1 and l2 capsid proteins of bovine papillomavirus type 1.encapsidation of circular dna by papillomavirus capsid protein was investigated in cos-1 cells. plasmids carrying both an sv40 origin of replication (ori) and an e. coli ori were introduced into cos-1 cells by dna transfection pv capsid proteins were supplied in trans by recombinant vaccinia viruses. pseudovirions were purified from infected cells and their packaged dna was extracted and used to transform e. coli as an indication of packaging efficacy. vlps assembled from bpv-1 l1 alone packaged ...19989568045
calcium is required in reassembly of bovine papillomavirus in vitro.papillomaviruses are small dna viruses which infect and induce benign warts and sometimes malignant tumours in the epithelium of the skin or mucosa. the viruses do not replicate in conventional tissue culture systems and little is known about the requirements for virus assembly. we investigated the effect of ethylene glycol-bis(aminoethyl ether)-tetraacetic acid (egta) and dithiothreitol (dtt) treatment on the stability of bovine papillomavirus type 1 (bpv-1) particles in vitro. removal of calci ...19989603328
significant behavioral recovery in parkinson's disease model by direct intracerebral gene transfer using continuous injection of a plasmid dna-liposome an alternative to virus-mediated gene transfer, we previously demonstrated a simple, safe, and efficient transfer of foreign gene into the central nervous system using continuous injection of a plasmid dna-cationic liposome complex. to explore whether this approach can be applied to the treatment of certain neurological disorders, we used an experimental model of parkinson's disease (pd) in the present study. following continuous injection for 7 days, tyrosine hydroxylase (th) and aromatic l- ...19989607420
distinct roles of two binding sites for the bovine papillomavirus (bpv) e2 transactivator on bpv dna replication.the modulation of dna replication by transcription factors was examined by using bovine papillomavirus type 1 (bpv). bpv replication in vivo requires two viral proteins: e1, an origin-binding protein, and e2, a transcriptional transactivator. in the origin, e1 interacts with a central region flanked by two binding sites for e2 (bs11 and bs12), of which only bs12 has been reported to be essential for replication in vivo. using chemical interference and electrophoretic mobility shift assays, we fo ...19989621032
the bpv-4 co-carcinogen quercetin induces cell cycle arrest and up-regulates transcription from the lcr of bpv-4.bracken fern is the environmental co-carcinogen of bpv-4 in the induction of neoplasias of the upper alimentary canal of cattle. the flavonoid quercetin is one of the most potent and best characterised mutagens present in the fern. we have shown that transfection with bpv-4 dna and exposure to a single dose of quercetin leads to tumorigenic transformation of primary bovine cells. we now show that quercetin induces cell cycle arrest and up-regulates transcription from the bpv-4 long control regio ...19989652740
p53 protein is a suppressor of papillomavirus dna amplificational replication.p53 protein was able to block human and bovine papillomavirus dna amplificational replication while not interfering with epstein-barr virus orip once-per-cell cycle replication. oligomerization, intact dna-binding, replication protein a-binding, and proline-rich domains of the p53 protein were essential for efficient inhibition, while the n-terminal transcriptional activation and c-terminal regulatory domains were dispensable for the suppressor activity of the p53 protein. the inhibition of repl ...19989658131
the papillomavirus e1 protein forms a dna-dependent hexameric complex with atpase and dna helicase activities.the e1 protein from bovine papillomavirus has site-specific dna binding activity, dna helicase activity, and dna-dependent atpase activity consistent with the properties of an initiator protein. here we have identified and characterized a novel oligomeric form of e1 that is associated with the atpase and dna helicase activities and whose formation is strongly stimulated by single-stranded dna. this oligomeric form corresponds to a hexamer of e1.19989658141
interaction of prion peptide huprp106-126 with nucleic acid.synthetic prion peptide prp106-126 has been used as a model to understand prion diseases. the conformation of the peptide depends on the environmental conditions and it forms amyloid in vitro. the potential of this prion peptide to interact with nucleic acids has been studied using a fluorescent labelled nucleic acid by kinetic and equilibrium methods. a decrease in the fluorescence of the labelled dna induced by the peptide with time is observed which is ph, ionic strength and temperature depen ...19979672613
two antibodies that neutralize papillomavirus by different mechanisms show distinct binding patterns at 13 a resolution.complexes between bovine papillomavirus type 1 (bpv1) and examples of two sets of neutralizing, monoclonal antibodies (mab) to the major capsid protein (l1) were analyzed by low-dose cryo-electron microscopy and three-dimensional (3d) image reconstruction to 13 a resolution. mab #9 is representative of a set of neutralizing antibodies that can inhibit viral binding to the cell surface, while mab 5b6 is representative of a second set that efficiently neutralizes papillomaviruses without significa ...19989680478
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
1h, 15n, and 13c nmr resonance assignments for the dna-binding domain of the bpv-1 e2 protein. 19989691287
functional interaction between the bovine papillomavirus virus type 1 replicative helicase e1 and cyclin e-cdk2.we have found that the replicative helicase e1 of bovine papillomavirus type 1 (bpv-1) interacts with a key cell cycle regulator of s phase, the cyclin e-cdk2 kinase. the e1 helicase, which interacts with cyclin e and not with cdk2, presents the highest affinity for catalytically active kinase complexes. in addition, e1, cyclin e, and cdk2 expressed in xenopus egg extracts are quantitatively coimmunoprecipitated from crude extracts by either anti-cdk2 or anti-e1 antibodies. e1 protein is also a ...19989696820
subpopulations of lymphocytes in cattle naturally infected with papillomavirus.subpopulations of blood lymphocytes (cd2, cd4, cd8, wc1 and igm-mu chain) were evaluated in clinically manifested bovine papillomatosis. significantly lower numbers of cd2 (44.7%), cd4 (22.8%) and a lower ratio of cd4/cd8 (1.5) were found in animals with tumours compared to a group of cattle free of papillomas (62.3%, 34%, and 2.3, respectively). on the other hand, significantly higher numbers of gamma/delta+ t lymphocytes (9.6%) and of lymphocytes expressing igm molecules (35%) were observed in ...19989704506
bovine papillomavirus transmission and chromosomal aberrations: an experimental model.enzootic haematuria and urinary bladder cancer in cattle are associated with feeding on bracken fern and bovine papillomavirus (bpv) infection. an increased rate of chromosomal aberrations in peripheral blood lymphocytes from chronically affected haematuric cows raised in bracken fern pastures has been reported, suggesting the presence of bpv in the peripheral blood of afflicted animals. the purpose of the present investigation was to examine the role of peripheral blood as a potential bpv-trans ...19989747721
role of glutamine 17 of the bovine papillomavirus e5 protein in platelet-derived growth factor beta receptor activation and cell transformation.the bovine papillomavirus e5 protein is a small, homodimeric transmembrane protein that forms a stable complex with the cellular platelet-derived growth factor (pdgf) beta receptor through transmembrane and juxtamembrane interactions, resulting in receptor activation and cell transformation. glutamine 17 in the transmembrane domain of the 44-amino-acid e5 protein is critical for complex formation and receptor activation, and we previously proposed that glutamine 17 forms a hydrogen bond with thr ...19989765437
a pyrimidine-rich exonic splicing suppressor binds multiple rna splicing factors and inhibits spliceosome assembly.the bovine papillomavirus type 1 (bpv-1) exonic splicing suppressor (ess) is juxtaposed immediately downstream of bpv-1 splicing enhancer 1 and negatively modulates selection of a suboptimal 3' splice site at nucleotide 3225. the present study demonstrates that this pyrimidine-rich ess inhibits utilization of upstream 3' splice sites by blocking early steps in spliceosome assembly. analysis of the proteins that bind to the ess showed that the u-rich 5' region binds u2af65 and polypyrimidine trac ...19989826658
structural code for dna recognition revealed in crystal structures of papillomavirus e2-dna targets.transcriptional regulation in papillomaviruses depends on sequence-specific binding of the regulatory protein e2 to several sites in the viral genome. crystal structures of bovine papillomavirus e2 dna targets reveal a conformational variant of b-dna characterized by a roll-induced writhe and helical repeat of 10.5 bp per turn. a comparison between the free and the protein-bound dna demonstrates that the intrinsic structure of the dna regions contacted directly by the protein and the deformabili ...19989860945
bovine papillomavirus e5 protein induces oligomerization and trans-phosphorylation of the platelet-derived growth factor beta receptor.the bovine papillomavirus e5 protein is a 44-aa transmembrane protein that forms a stable complex with the cellular platelet-derived growth factor (pdgf) beta receptor and induces constitutive tyrosine phosphorylation and activation of the receptor, resulting in cell transformation. the e5 protein does not resemble pdgf, but rather activates the receptor in a ligand-independent fashion, thus providing a unique system to examine activation of receptor tyrosine kinases. here, we used a variety of ...19989860953
inhibition/stimulation of bovine papillomavirus by adeno-associated virus is time as well as multiplicity dependent.infection by adeno-associated virus (aav) is associated with lower cervical cancer rates. we have been investigating the hypothesis that aav interacts with and inhibits the role of human papillomaviruses (hpv) in cervical cancer. we have been studying the response of bovine papillomavirus type 1 (bpv) oncogenic transformation and dna replication to aav as a prototype system. the aav rep 78 gene product is responsible for this inhibition. here, it is demonstrated that in two assay systems, focus ...19989705917
function of a bovine papillomavirus type 1 exonic splicing suppressor requires a suboptimal upstream 3' splice site.alternative splicing is an important mechanism for the regulation of bovine papillomavirus type 1 (bpv-1) gene expression during the virus life cycle. previous studies in our laboratory have identified two purine-rich exonic splicing enhancers (eses), se1 and se2, located between two alternative 3' splice sites at nucleotide (nt) 3225 and nt 3605. further analysis of bpv-1 late-pre-mrna splicing in vitro revealed a 48-nt pyrimidine-rich region immediately downstream of se1 that inhibits utilizat ...19999847303
dna curvature and deformation in protein-dna complexes: a step in the right direction. 19989860938
mucosal immunisation with papillomavirus virus-like particles elicits systemic and mucosal immunity in has been shown previously that recombinant virus-like particles (vlps) of papillomavirus can induce vlp-specific humoral and cellular immune responses following parenteral administration. to test whether mucosal administration of bovine papillomavirus type 1 (bpv1) vlps could produce mucosal as well as systemic immune responses to vlps, 50 micrograms chimeric bpv1 vlps containing an hpv16 e7 ctl epitope (bpvl1/e7 vlp) was administered intranasally to mice. after two immunisations, l1-specific ...19989875315
virocrine transformation: the intersection between viral transforming proteins and cellular signal transduction pathways.this review describes a mechanism of viral transformation involving activation of cellular signaling pathways. we focus on four viral oncoproteins: the e5 protein of bovine papillomavirus, which activates the platelet-derived growth factor beta receptor; gp55 of spleen focus forming virus, which activates the erythropoietin receptor; polyoma virus middle t antigen, which resembles an activated receptor tyrosine kinase; and lmp-1 of epstein-barr virus, which mimics an activated tumor necrosis fac ...19989891803
a broad-spectrum microbicide with virucidal activity against sexually transmitted viruses.sodium dodecyl sulfate (sds), an alkyl sulfate surfactant derived from an organic alcohol, possesses surfactant properties but also denatures and unfolds both monomeric and subunit proteins. in preliminary experiments, we demonstrated that sds is a potent inactivator of herpes simplex virus type 2 and human immunodeficiency virus type 1 at concentrations comparable to those used for the surfactant nonoxynol-9. we hypothesized that sds might be capable of denaturing the capsid proteins of nonenve ...19999925525
biochemical and electron microscopic image analysis of the hexameric e1 helicase.dna replication initiator proteins bind site specifically to origin sites and in most cases participate in the early steps of unwinding the duplex. the papillomavirus preinitiation complex that assembles on the origin of replication is composed of proteins e1 and the activator protein e2. e2 is an ancillary factor that increases the affinity of e1 for the ori site through cooperative binding. here we show that duplex dna affects e1 (in the absence of e2) to assemble into an active hexameric stru ...19999933649
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
the bovine papillomavirus type 1 e6 oncoprotein sensitizes cells to tumor necrosis factor alpha-induced apoptosis.expression of viral proteins may result in susceptibility of cells to the cytotoxic effect of tumor necrosis factor alpha (tnf). while murine c127 cells containing the bovine papillomavirus type 1 (bpv-1) genome were reported to exhibit increased tnf sensitivity, the gene(s) responsible was not identified. the bpv-1 e6 oncoprotein induces tumorigenic transformation of murine c127 cells and stimulates transcription when targeted to a promoter. bpv-1 e6 was introduced into c127 cells (pbe6) by ret ...19999989810
characteristics of cytosine deaminase-5-fluorocytosine system. enhancement of radiation cytotoxicity and bystander effect. 199810026860
induction of autoantibodies to mouse ccr5 with recombinant papillomavirus particles.the vertebrate immune system has evolved to respond vigorously to microbial infection but to ignore self-antigens. evidence has emerged that b cell responses to viruses are initiated by immune recognition of ordered arrays of antigen on the viral surface. to test whether autoantibodies against a self-antigen can be induced by placing it in a context that mimics the ordered surface of a viral particle, a peptide representing an extracellular loop of the mouse chemokine receptor ccr5 was incorpora ...199910051649
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
rat embryo fibroblasts transformed by c-jun display highly metastatic and angiogenic activities in vivo and deregulate gene expression of both angiogenic and antiangiogenic factors.the comparative tumorigenicity in rats and nude mice of cell lines derived from fr3t3 and transformed by either c-jun, ras, sv40 lt, or bovine papilloma virus type 1 (bpv1) oncogenes was investigated. c-jun-transformed cells were as tumorigenic and metastatic as ras-transformed cells. latencies were short, and numerous pulmonary metastases were observed in all injected animals. in contrast, tumors induced by s.c. injection of sv40-transformed cells developed slower, and none of the animals who r ...199910099833
long-term episomal maintenance of bovine papillomavirus type 1 plasmids is determined by attachment to host chromosomes, which is mediated by the viral e2 protein and its binding sites.papillomavirus genomes are stably maintained as extrachromosomal nuclear plasmids in dividing host cells. to address the mechanisms responsible for stable maintenance of virus, we examined nuclear compartmentalization of plasmids containing the full-length upstream regulatory region (urr) from the bovine papillomavirus type 1 (bpv1) genome. we found that these plasmids are tightly associated with the nuclear chromatin both in the stable cell lines that maintain episomal copies of the plasmids an ...199910196338
persistent expression of foreign genes in cultured hepatocytes: expression vectors.we have optimized a liposome-based transfection method that mediated highly efficient stable expression of foreign genes in hepatocytes. moreover, we have observed that the metallothionein 1 promoter in the bovine papilloma virus-based expression vector drove the highest expression of foreign genes in hepatocytes as compared with the cytomegalovirus and the human polypeptide chain elongation factor 1alpha (ef-1alpha) promoters in the pcdna 3-based expression vector. the cytomegalovirus promoter ...199910196472
effect of bovine papillomavirus e2 protein-specific monoclonal antibodies on papillomavirus dna replication.the bovine papillomavirus type 1 (bpv-1) e2 protein is the master regulator of papillomavirus replication and transcription. we have raised a panel of monoclonal antibodies (mabs) against the bpv-1 e2 protein and used them to probe the structure and function of the protein. five mabs reacted with linear epitopes, and four mabs recognized conformation-dependent epitopes which mapped within the c-terminal dna-binding and dimerization domain. mab 1e2 was able to recognize the replication- and trans ...199910233926
papillomavirus capsid protein expression level depends on the match between codon usage and trna availability.translation of mrna encoding the l1 and l2 capsid proteins of papillomavirus (pv) is restricted in vivo to differentiated epithelial cells, although transcription of the l1 and l2 late genes occurs more widely. the codon composition of pv late genes is quite different from that of most mammalian genes. to test the possibility that pv late gene codon composition determines the efficiency of pv late gene expression in some cell types, synthetic bovine papillomavirus type 1 (bpv1) late genes were c ...199910233959
nucleotides 1506-1625 of bovine papillomavirus type 1 genome can enhance dna packaging by l1/l2 capsids.we have previously described a dna-packaging assay using bovine papillomavirus type 1 (bpv-1) virus-like particles (vlps) and have identified a region of the bpv genome that assists in packaging. in this study, we identify a specific bpv sequence involved in dna packaging by bpv-1 vlps. in the initial screening of bpv-1 genomic sequences essential for dna packaging, we observed that a plasmid with deletions between nucleotides (nt) 948 and 2113 failed to be packaged into bpv-1 vlps. however, pla ...199910364505
role of the atp-binding domain of the human papillomavirus type 11 e1 helicase in e2-dependent binding to the origin.replication of the genome of human papillomaviruses (hpv) is initiated by the recruitment of the viral e1 helicase to the origin of dna replication by the viral e2 protein, which binds specifically to the origin. we determined, for hpv type 11 (hpv-11), that the c-terminal 296 amino acids of e1 are sufficient for interaction with the transactivation domain of e2 in the yeast two-hybrid system and in vitro. this region of e1 encompasses the atp-binding domain. here we have examined the role of th ...199910364274
high precision solution structure of the c-terminal kh domain of heterogeneous nuclear ribonucleoprotein k, a c-myc transcription factor.among it's many reported functions, heterogeneous nuclear ribonucleoprotein (hnrnp) k is a transcription factor for the c- myc gene, a proto-oncogene critical for the regulation of cell growth and differentiation. we have determined the solution structure of the gly26-->arg mutant of the c-terminal k-homology (kh) domain of hnrnp k by nmr spectroscopy. this is the first structure investigation of hnrnp k. backbone residual dipolar couplings, which provide information that is fundamentally differ ...199910369774
nucleotide sequence and characterization of human papillomavirus type 83, a novel genital papillomavirus.studies of human papillomaviruses (hpv) are hampered by the lack of a conventional culture system, because hpv completes its life cycle only in fully differentiated human tissue. to overcome this obstacle, the athymic mouse xenograft system has been used to study the pathogenesis of a limited number of hpv types. we recently reported the propagation of a novel hpv type in the mouse xenograft system and the cloning of its genome. consensus primer pcr had previously identified this virus as mm7, l ...199910405368
papillomavirus e2 induces p53-independent apoptosis in hela cells.we have previously shown that expression of the papillomavirus e2 protein in hela cells induces p53 accumulation and causes both cell cycle arrest and apoptosis. in contrast to growth arrest, onset of apoptosis was not correlated with an increase of p53 transcriptional activity. in the present study, we conducted biochemical and genetic experiments in order to determine whether e2-induced apoptosis was independent of p53 induction. we showed that e2 did not alter the transcription of bax, a know ...199910467398
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
bovine papillomaviral gene expression in equine sarcoid tumours.the sarcoid is a benign locally invasive dermal fibroblastic lesion, commonly affecting horses and donkeys. the aetiology of the equine sarcoid is equivocal. bovine papillomaviral (bpv) dna (type 1/2) is frequently demonstrable in equine sarcoid tumour biopsies. however, the exact role of the virus in the disease process and its contribution to the phenotypic differences in sarcoids is not known. it was sought to assess the transcriptional activity of bpv-1 found in sarcoid tissues. of 20 tumour ...199910475087
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
binding of the human papillomavirus type 16 p97 promoter by the adeno-associated virus rep78 major regulatory protein correlates with inhibition.human papillomavirus type 16 (hpv-16) infection is positively associated with cervical cancer, whereas adeno-associated virus (aav) infection is negatively associated with this same cancer. in earlier studies these two virus types have been shown to directly interact, with aav inhibiting or enhancing papillomavirus functions depending upon the specific circumstances. one defined interaction between these two viruses is the ability of the aav rep78 major regulatory protein to inhibit gene express ...199910531369
mutation correction by homologous recombination with an adenovirus vector. 200010561834
protein-sulfenic acids: diverse roles for an unlikely player in enzyme catalysis and redox regulation.while it has been known for more than 20 years that unusually stable cysteine-sulfenic acid (cys-soh) derivatives can be introduced in selected proteins by mild oxidation, only recently have chemical and crystallographic evidence for functional cys-soh been presented with native proteins such as nadh peroxidase and nadh oxidase, nitrile hydratase, and the horf6 and ahpc peroxiredoxins. in addition, cys-soh forms of protein tyrosine phosphatases and glutathione reductase have been suggested to pl ...199910569923
two distinct regions of the bpv1 e1 replication protein interact with the activation domain of e2.papillomavirus e1 and e2 proteins co-operation in viral dna replication is mediated by protein-protein interactions that lead to formation of an e1-e2 complex. to identify the domains involved, portions of the two proteins were expressed as fusions to the dna-binding protein lexa or the transactivation domain of vp16 and analyzed by the yeast two-hybrid system. the c-terminal 266 amino acids of bpv1 e1 (e1c266) interacted strongly with e2 in the yeast system and in a mammalian two-hybrid assay. ...199910581387
structural correlates for enhanced stability in the e2 dna-binding domain from bovine papillomavirus.papillomaviral e2 proteins participate in viral dna replication and transcriptional regulation. we have solved the solution structure of the dna-binding domain of the e2 protein from bovine papillomavirus (bpv-1). the structure calculation used 2222 distance and 158 dihedral angle restraints for the homodimer (202 residues in total), which were derived from homonuclear and heteronuclear multidimensional nuclear magnetic resonance (nmr) spectroscopic data. the root-mean-square deviation for struc ...199910587434
the differentiation-specific factor cdp/cut represses transcription and replication of human papillomaviruses through a conserved silencing element.the life cycles of human papillomaviruses (hpvs) are intimately linked to the differentiation program of infected stratified epithelia, with both viral gene expression and replication being maintained at low levels in undifferentiated basal cells and increased upon host cell differentiation. we recently identified, in hpv-16, a negative regulatory element between the epithelial-cell-specific enhancer and the e6 promoter that is capable of silencing e6 promoter activity, and we termed this elemen ...200010590129
a method for efficient extraction of bovine papilloma virus-based minichromosomes that preserves native chromatin structure.aiming to create an adequate model for investigation of the molecular mechanisms involved in transcriptional regulation by steroid hormones, a number of cell lines carrying bovine papilloma virus (bpv) based constructs containing the mouse mammary tumor virus long terminal repeat (ltr) were established (ostrowski et al., mol. cell. biol. 3, 2945-2957, 1983). however, all our attempts to extract from the cells such minichromosomes as nucleoprotein complexes using a method previously described (os ...199910619601
identification of a second transforming function in bovine papillomavirus type 1 e6 and the role of e6 interactions with paxillin, e6bp, and e6ap.papillomavirus e6 oncoproteins transform mammalian cells through interaction with cellular proteins. bovine papillomavirus type 1 e6 (be6) interacts with three previously described cellular targets: the e6ap e3 ubiquitin ligase, the calcium-binding protein e6bp (also known as erc-55), and paxillin, which is a focal adhesion adapter protein. be6 interacts strongly with each of these proteins in vitro, binding to similar peptide sequences found in e6ap, e6bp, and paxillin. to determine which be6 i ...200010623743
identification of a short, hydrophilic amino acid sequence critical for origin recognition by the bovine papillomavirus e1 protein.the e1 protein of bovine papillomavirus (bpv) is a site-specific dna binding protein that recognizes an 18-bp inverted repeat element in the viral origin of replication. sequence-specific dna binding function maps to the region from approximately amino acids 140 to 300, and isolated polypeptides containing this region have been shown to retain origin binding in vitro. to investigate the sequence and structural characteristics which contribute to sequence-specific binding, the primary sequence of ...200010590112
two patches of amino acids on the e2 dna binding domain define the surface for interaction with e1.the e1 and e2 proteins from bovine papillomavirus bind cooperatively to the viral origin of dna replication (ori), forming a complex which is essential for initiation of dna replication. cooperative binding has two components, in which (i) the dna binding domains (dbds) of the two proteins interact with each other and (ii) the e2 transactivation domain interacts with the helicase domain of e1. by generating specific point mutations in the dbd of e2, we have defined two patches of amino acids tha ...200010627562
adeno-associated virus rep78 binds to e2-responsive element 1 of bovine papillomavirus type 1.adeno-associated virus type-2 (aav-2) is a helper-dependent parvovirus that has been implicated in the inhibition of replication and oncogenic transformation of bovine papillomavirus type-1 (bpv-1) and other transforming dna viruses. previous studies have suggested that the rep78 protein of aav-2 is a key player mediating this effect. in this report we have analyzed the effect of aav-2 rep78 protein on the regulation of gene expression of a reporter gene under the control of the long control reg ...199910632568
stable maintenance of linear bovine papillomavirus 1 molecules in c127i cells.this paper describes the characterization of cell lines that stably maintain linear copies of bovine papillomavirus 1 (bpv-1). cell lines were generated by liposome-mediated transfection of bamh1-linearized virus into c127i cells. two transfectants with morphologies differing from each other and from that of the parental cell line were characterized. southern blots indicated that they contain ten to twelve copies of the bpv-1 genome per cell and that the predominant species in both cell lines ar ...199910643966
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
golgi alkalinization by the papillomavirus e5 oncoprotein.the e5 oncoprotein of bovine papillomavirus type i is a small, hydrophobic polypeptide localized predominantly in the golgi complex. e5-mediated transformation is often associated with activation of the pdgf receptor (pdgf-r). however, some e5 mutants fail to induce pdgf-r phosphorylation yet retain transforming activity, suggesting an additional mechanism of action. since e5 also interacts with the 16-kd pore-forming subunit of the vacuolar h(+)-atpase (v-atpase), the oncoprotein could conceiva ...200010648563
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
a structural model for the rola protein and its interaction with dna.the study of the plant oncogene rola has been hampered by a lack of structural information. here we show that, despite a lack of significant sequence similarity to proteins of known structure, the rola sequence adopts a known fold; that of the papillomavirus e2 dna-binding domain. this fold is reliably identified by modern threading programs, which consider predicted secondary structure, but not by others. although the rola sequence is only around 16% identical to those of the available template ...199910651283
transcription factor-dependent loading of the e1 initiator reveals modular assembly of the papillomavirus origin melting complex.replication of bovine papillomavirus type 1 dna absolutely requires the viral transcription factor e2 as well as the initiator e1, although e1 alone has all the activities expected of an initiator protein. e1 assembles on the dna in a stepwise fashion and undergoes a transition in activities from site-specific dna-binding protein to mobile helicase. complex assembly is assisted by the viral transcription factor e2 at two levels. e2 acts generally as a specificity factor, which through cooperativ ...200010652347
inhibition of the bovine papillomavirus e2 protein activity by peptide nucleic acid.the bovine papillomavirus type-1 e2 protein is the master regulator of the papillomavirus transcription and replication, the activity of which is regulated through sequence-specific dna binding. peptide nucleic acid (pna) is a nucleic acid analogue, which associates with high affinity to complementary dna, rna or pna, yielding in formation of stable complexes. the potential use of pna as a sequence-specific inhibitor of the e2 protein activity is studied in this report. we demonstrate that repla ...200010653916
position-dependent inhibition of the cleavage step of pre-mrna 3'-end processing by u1 snrnp.the 3' ends of most eukaryotic pre-mrnas are generated by 3' endonucleolytic cleavage and subsequent polyadenylation. 3'-end formation can be influenced positively or negatively by various factors. in particular, u1 snrnp acts as an inhibitor when bound to a 5' splice site located either upstream of the 3'-end formation signals of bovine papilloma virus (bpv) late transcripts or downstream of the 3'-end processing signals in the 5' ltr of the hiv-1 provirus. previous work showed that in bpv it i ...200010688357
parameters that affect in vitro splicing of bovine papillomavirus type 1 late pre-mrnas.during the course of study on regulated viral pre-mrna splicing, an in vitro rna splicing assay was developed to analyze how an exonic splicing enhancer stimulates splicing of bovine papillomavirus type 1 (bpv-1) late pre-mrnas. the optimal concentration of hela nuclear extract (hne) in a standard rna splicing reaction depends on the individual substrate pre-mrna. splicing of a bpv-1 late pre-mrna required 40% hne and 2 h incubation at 30 degrees c. higher hne was detrimental to splicing and lon ...200010716353
bovine papillomavirus e5 protein induces the formation of signal transduction complexes containing dimeric activated platelet-derived growth factor beta receptor and associated signaling proteins.the bovine papillomavirus e5 protein binds to the cellular platelet-derived growth factor (pdgf) beta receptor, resulting in constitutive activation of the receptor and cell growth transformation. by subjecting extracts from e5-transformed or pdgf-treated cells to velocity sedimentation in sucrose gradients, activated pdgf beta receptor complexes were separated from monomeric, inactive receptor. rapidly sedimenting activated complexes contained oligomeric (apparently dimeric), tyrosine-phosphory ...200010734138
interaction of the papillomavirus e2 protein with mitotic chromosomes.the bovine papillomavirus e2 transactivator protein is a multifunctional protein that activates viral transcription, cooperates in initiation of viral dna replication, and is required for long-term episomal maintenance of viral genomes. we have shown previously that the e2 transactivator protein and bovine papillomavirus type 1 genomes are associated with mitotic chromosomes and have proposed that e2 links the genomes to cellular chromosomes to ensure segregation to daughter nuclei. in this stud ...200010772985
cell-specific modulation of papovavirus replication by tumor suppressor protein p53.small dna tumor viruses like human papillomaviruses, simian virus 40, and adenoviruses modulate the activity of cellular tumor suppressor proteins p53 and/or prb. these viruses replicate as nuclear multicopy extrachromosomal elements during the s phase of the cell cycle, and it has been suggested that inactivation of p53 and prb is necessary for directing the cells to the s phase. mouse polyomavirus (py), however, modulates only the prb protein activity without any obvious interference with the ...200010775606
the bovine papillomavirus e2 transactivator is stimulated by the e1 initiator through the e2 activation domain.bovine papillomavirus type 1 (bpv-1) encodes two regulatory proteins, e1 and e2, that are essential for viral replication and transcription. e1, an atp-dependent helicase, binds to the viral ori and is essential for viral replication, while the viral transcriptional activator, e2, plays cis-dominant roles in both viral replication and transcription. at low reporter concentrations, e1 stimulates e2 enhancer function, while at high reporter concentrations, repression results. an analysis of cis re ...200010793002
production of infectious bovine papillomavirus from cloned viral dna by using an organotypic raft/xenograft technique.bovine papillomavirus type 1 (bpv-1) induces fibropapillomas in its natural host and can transform fibroblasts in culture. the viral genome is maintained as an episome within fibroblasts, which has allowed extensive genetic analyses of the viral functions required for dna replication, gene expression, and transformation. much less is known about bpv-1 gene expression and replication in bovine epithelial cells because the study of the complete viral life cycle requires an experimental system capa ...200010805809
expression vector with dna of bovine papilloma virus 1 for keratinocyte gene therapy.although there are several methods for introducing the genes to keratinocytes in vivo, expression of transgene does not last long enough for effective keratinocyte gene therapy. in this study, we added bovine papilloma virus 1 (bpv) dna into expression vectors with the lacz gene driven by metallothionein and keratin 10 promoters, and we transferred them into keratinocytes in vivo using the naked dna method, and measured beta-gal activity in keratinocytes. the results showed that beta-galactosida ...200010808128
amf-1/gps2 binds p300 and enhances its interaction with papillomavirus e2 proteins.the cellular protein amf-1 (gps2) positively modulates gene expression by the papillomavirus e2 protein (d. e. breiding et al., mol. cell. biol. 17:7208-7219, 1997). we show here that amf-1 also binds the transcriptional coactivator p300 in vitro and in vivo. e2 interacted weakly with p300. these observations led to a model in which amf-1 recruits p300 into a complex with e2. cotransfection of amf-1 or p300 stimulated levels of e2-dependent transcription, while cotransfection of both amf-1 and p ...200010846067
optimization of a weak 3' splice site counteracts the function of a bovine papillomavirus type 1 exonic splicing suppressor in vitro and in vivo.alternative splicing is a critical component of the early to late switch in papillomavirus gene expression. in bovine papillomavirus type 1 (bpv-1), a switch in 3' splice site utilization from an early 3' splice site at nucleotide (nt) 3225 to a late-specific 3' splice site at nt 3605 is essential for expression of the major capsid (l1) mrna. three viral splicing elements have recently been identified between the two alternative 3' splice sites and have been shown to play an important role in th ...200010846071
proteasome-mediated degradation of the papillomavirus e2-ta protein is regulated by phosphorylation and can modulate viral genome copy number.the bovine papillomavirus e2 proteins regulate viral transcription, replication, and episomal genome maintenance. we have previously mapped the major phosphorylation sites of the e2 proteins to serine residues 298 and 301 and shown that mutation of serine residue 301 to alanine leads to a dramatic (10- to 20-fold) increase in viral dna copy number. in this study we analyzed how phosphorylation regulates e2 protein function. s301 is located in a pest sequence; these sequences are often found in p ...200010846085
separate domains in e1 and e2 proteins serve architectural and productive roles for cooperative dna binding.the e1 and e2 proteins from bovine papillomavirus bind cooperatively to binding sites in the viral origin of dna replication. the dna-binding domains (dbds) of the two proteins interact with each other, and the e2 transactivation domain interacts with the helicase domain of e1. mutations that disrupt the interaction between the two dbds also disrupt the interaction between the e2 activation domain and the e1 helicase domain, demonstrating interdependence of the two interactions. cooperative bind ...200010856250
in vitro determination of carcinogenicity of sixty-four compounds using a bovine papillomavirus dna-carrying c3h/10t(1/2) cell line.a new in vitro test for predicting rodent carcinogenicity is evaluated against a testing database of 64 chemicals including both genotoxic and nongenotoxic carcinogens and carcinogens that normally require addition of an s-9 microsomal fraction for detection in the bacterial mutagenicity assay. the assay uses focus formation in a stable, bovine papillomavirus type 1 (bpv-1) dna carrying c3h/10t(1/2) mouse embryo fibroblast cell line (t1) that does not require transfection, infection with virus, ...200010861948
contribution of bovine papillomavirus type 1 e1 protein residue 48 to replication function.the e1 protein of bovine papillomavirus type 1 (bpv-1) is the origin recognition protein and is essential for the initiation of viral dna replication. we reported previously that there is a conserved motif between residues 25 and 60 of all papillomavirus e1 proteins that resembles a casein kinase ii (ckii) phosphorylation site. the corresponding serine in bpv-1, serine-48, is an efficient substrate for ckii in vitro. to examine the functional role of this potential phosphorylation site, three am ...200010900038
bovine papillomavirus e1 protein is sumoylated by the host cell ubc9 protein.papillomavirus e1 protein is the replication initiator that recognizes and binds to the viral origin and initiates dna strand separation through its atp-dependent helicase activity. the e1 protein also functions in viral dna replication by recruiting several cellular proteins to the origin, including host dna polymerase alpha and replication protein a. to identify other cellular proteins that interact with bovine papillomavirus e1, an hela cdna library was screened using a yeast two-hybrid assay ...200010871618
bpv1 e2 protein enhances packaging of full-length plasmid dna in bpv1 pseudovirions.we studied determinants of efficient encapsidation of circular dna, incorporating a pv early region dna sequence (nt 584-1978) previously shown to enhance packaging of dna within papillomavirus (pv)-like particles (vlps). insect coelomic cells (sf-9) and cultured monkey kidney cells (cos-1) were transfected with an 8-kb reporter plasmid incorporating the putative bpv packaging sequence and infected with bpv1 l1 and l2 recombinant baculovirus or vaccinia virus. heavy (1.34 g/ml) and light (1.30 g ...200010873782
rb-independent induction of apoptosis by bovine papillomavirus type 1 e7 in response to tumor necrosis factor alpha.bovine papillomavirus type 1 (bpv-1) is a small dna virus that causes fibropapillomas of the host. bpv-1 has served as the prototype for studies of the molecular biology of the papillomaviruses. bpv-1 efficiently induces anchorage-independent growth and focus formation in murine c127 cells. the transforming properties of bpv-1 primarily reside in two genes, e5 and e6. each of these genes is sufficient to transform cells. although no independent transformation activity has been detected for e7, i ...200010887172
papillomavirus virus-like particles for the delivery of multiple cytotoxic t cell epitopes.chimeric papillomavirus (pv) virus-like particles (vlps) based on the bovine papillomavirus type 1 (bpv-1) l1 protein were constructed by replacing the 23-carboxyl-terminal amino acids of the bpv1 major protein l1 with an artificial "polytope" minigene, containing known ctl epitopes of human pv16 e7 protein, hiv iiib gp120 p18, nef, and reverse transcriptase (rt) proteins, and an hpv16 e7 linear b epitope. the ctl epitopes were restricted by three different mhc class i alleles (h-2(b), h-2(d), h ...200010915608
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