Publications

dna sequence of the hpv-16 e5 orf and the structural conservation of its encoded protein.	infection of cervical epithelium by human papillomavirus type 16 (hpv-16) appears to be closely associated with the development of cervical dysplasia and carcinoma. by inference from genetic and biochemical studies of the bovine papillomavirus, the e5 orf of the human papillomaviruses is anticipated to encode a "transforming" protein. in an effort to compare the e5 orf of hpv-16 with other human papillomaviruses and bovine papillomavirus, we sequenced this region from a new isolate of hpv-16 whi ...	1988	2831662
dna bending is induced in an enhancer by the dna-binding domain of the bovine papillomavirus e2 protein.	the e2 gene of bovine papillomavirus type 1 has been shown to encode a dna-binding protein and to trans-activate the viral enhancer. we have localized the dna-binding domain of the e2 protein to the carboxyl-terminal 126 amino acids of the e2 open reading frame. the dna-binding domain has been expressed in escherichia coli and partially purified. gel retardation and dnase i "footprinting" on the bovine papillomavirus type 1 enhancer identify the sequence motif accn6ggt (in which n = any nucleoti ...	1988	2831538
establishment of mouse cell lines which constitutively secrete large quantities of interleukin 2, 3, 4 or 5, using modified cdna expression vectors.	mouse cell lines of different lineages have been established which constitutively secrete large quantities of recombinant mouse interleukins (mil2, mil3, mil4 or mil5). an existing bovine papilloma virus-based expression vector, pbv-1mtha, was modified to allow transformed x63ag8-653 myeloma cells, nih 3t3 fibroblasts and c127 mammary tumor cells to stably carry multiple copies of the vector, to express the inserted cdna encoding a single interleukin constitutively, and to secrete the interleuki ...	1988	2831066
cis-acting negative control of dna replication in eukaryotic cells.	we show that in stable monkey cell lines, the replication of a chimeric sv40-bpv episomal replicon occurs once and only once per cell cycle. the copy number of this episome is stably maintained even when an excess of the limiting initiation factor t antigen is provided. these experiments therefore uncover a cis-acting negative control mechanism whereby replication control is not focused on limiting the activity of positive factors; rather, replication is permitted in unreplicated replicons but i ...	1988	2830984
secretion of soluble functional insulin receptors by transfected nih3t3 cells.	in order to determine whether the human insulin receptor ectodomain can be expressed as a functional protein, the coding regions for the transmembrane and cytoplasmic domain of a full-length human insulin receptor cdna were deleted by site-directed mutagenesis, and the resultant construct was inserted into a bovine papilloma virus vector under the control of the mouse metallothionein promoter. after transfection of mouse nih3t3 cells, a cell line secreting an insulin binding protein was isolated ...	1988	2830271
the bovine papillomavirus genome and its uses as a eukaryotic vector.		1987	2829815
integration and transcription of human papillomavirus type 6 recombinant dna in mouse cells.	human papillomavirus (hpv) dna is found in nature mostly in an episomal form. however, in permanent cell lines established from cervical carcinomas in which hpv sequences are present, they are usually integrated in the host genome. in vitro studies of hpv have been hampered because of the difficulty of stably maintaining hpv sequences in transfected cells. we have cloned the entire hpv6 genome into three vectors: pml2, a derivative of pbr322 lacking the "poison sequences"; p142-6, a plasmid cont ...	1987	2829459
hepatitis b virus suppresses expression of human beta-interferon.	to determine whether hepatitis b virus (hbv) regulates the expression of the human beta-interferon gene, a series of recombinant bovine papilloma virus plasmids containing the human interferon gene and various fragments of the hbv genome were constructed and used to transform c127 cells, a murine fibroblast line. analysis of the dna from transformed c127 cells indicated that the interferon gene was intact and that the plasmids replicated as stable multicopy elements. the 1828-base-pair bamhi hbv ...	1988	2829171
structure and genetic expression of papillomaviruses.	this article reviews the physical structures, genetic organization, expression, and regulation of papillomaviruses. in view of the extensive characterization of cellular transformation and viral functions that have been achieved in experimentally infected animals and in transformed cell cultures, the bovine papillomavirus type 1 (bpv-1) and shope cottontail rabbit papillomavirus (crpv) are compared and contrasted with the human papillomaviruses.	1987	2829072
papillomavirus in the vapor of carbon dioxide laser-treated verrucae.	vapor produced by the carbon dioxide laser during the vaporization of papillomavirus-infected verrucae was analyzed for viral dna content. two models were used for evaluation: an in vitro cutaneous bovine fibropapilloma and an in vivo human verruca model. four bovine fibropapillomas were exposed to various laser parameters with power densities of 38,200 to 130 w/cm2 and energy fluences of 3820 to 130 j/cm2. the generated vapor was collected in a chamber in line with a vacuum system. hybridizatio ...	1988	2828703
vaccines for latent viruses.	there are two traditional ways to modify a virus for immunization: (1) kill the virus or (2) use a live, attenuated virus. there are three modern ways to prepare vaccines: (1) extract and purify a part of the virus that is immunogenic, (2) synthesize a polypeptide immunogen piece of the virus, or (3) use recombinant deoxyribonucleic acid or gene splicing to prepare an immunogenic portion of the virus. the last three produce subunit vaccines that can be made to contain no deoxyribonucleic acid. t ...	1988	2828442
the bpv1-e2 trans-acting protein can be either an activator or a repressor of the hpv18 regulatory region.	the human papillomavirus 18 (hpv 18) long control region contains promoter and enhancer elements whose activity is restricted to several human cell lines of epithelial origin. this enhancer possesses a considerable constitutive activity which is further stimulated in the presence of the e2 trans-activating protein of bovine papillomavirus 1 (bpv1). surprisingly the same bpv1 protein strongly repressed transcription from the genuine hpv18 enhancer-promoter dna sequences. we suggest that binding o ...	1987	2828029
multiple cis-active elements in the long control region of bovine papillomavirus type 1 (bpv-1).	a 1.0 kb region of the bpv-1 genome (the long control region, lcr), contains controls for transcription and the origin of replication. transcription directed by the lcr is activated by the viral encoded e2 protein. to define the essential cis acting elements that are required to control transcription we have constructed a series of deletions throughout the lcr. we have identified three important domains in the lcr, two of which respond to e2. we have analysed the ability of small subcloned regio ...	1987	2827118
identification of the human papillomavirus e2 protein in genital tract tissues.	a 27-kilodalton protein representing approximately 60% of the e2 open reading frame of human papillomavirus type 6 (hpv-6) was synthesized in a bacterial expression system. affinity-purified polyclonal antibody to this protein detected the probable e2 gene product as a 50-kilodalton protein in most condylomas by western blot (immunoblot) analysis. the e2-positive condylomas were associated with hpv-6, hpv-11, hpv-16, or unidentified hpvs.	1988	2826817
detection of dna of human papillomavirus types 6/11 and 16/18 in cell scrapings of the uterine cervix by filter in situ hybridisation. correlation with cytology, colposcopy and histology.	the application of filter in situ hybridisation (fish) to detect the presence of the dna of human papillomavirus genotypes 6/11 and/or 16/18 in cell scrapings of the uterine cervix of 248 women in western australia is described. the results obtained by fish are related to cervical dysplasia as assessed by cytology, colposcopy and histology. the detection of hpv infection was more sensitive and specific by fish than by either histological/cytological evidence of an hpv cytopathic effect (koilocyt ...	1987	2826222
cis activation of the c-myc gene in bovine papilloma virus type 1/human c-myc hybrid plasmids.	the c-myc gene amplification observed in human tumors is likely to represent an activation mechanism aiming at an increased transcription level. in order to evaluate the biological significance of this amplification in the malignant transformation we have designed an experimental model that could possibly mimic this situation in vitro. we have constructed a series of plasmids which physically link the human c-myc gene to the bovine papilloma virus type 1 genome (bpv1) and therefore should be mai ...	1988	2826197
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 ...	1987	2825987
replication of plasmids derived from bovine papilloma virus type 1 and epstein-barr virus in cells in culture.	the major components encoded by bpv-1 and ebv that act in plasmid replication of these viral dnas in latently infected cells are now known. the minimal dna sequences required in cis have been delineated, and the genes whose products are required in trans have been identified. the only required trans-acting gene of ebv, ebna-1, has been shown to bind specifically to the cis-acting element, orip. the current advanced understanding of plasmid replication of mtdna and sv40 dna is likely to aid in th ...	1987	2825737
messenger rnas from the e1 region of bovine papillomavirus type 1 detected in virus-infected bovine cells.	bovine papillomavirus type 1 dna replicated to a high copy number in virus-infected bovine fibroblasts. infected bovine cells were therefore used as a source of rna for northern blotting analysis to search for viral transcripts hybridizing to the e1 gene region, implicated in viral dna replication. cytoplasmic polyadenylated rna preparations contained at least five different e1-region transcripts, ranging from 1200 to approximately 4500 nucleotides in length. all of these species contained seque ...	1987	2825116
cloning and characterization of a papillomavirus associated with papillomas and carcinomas in the european harvest mouse (micromys minutus).	individuals in a colony of european harvest mice (micromys minutus) were diagnosed with a variety of skin tumors including papillomas, trichoepitheliomas, and sebaceous carcinomas. papillomavirus group-specific antigens and viruslike particles were detected in the papillomas. a 7.6-kilobase supercoiled circular dna, which was cleaved once by ecori, was visualized in papilloma extracts by low-stringency southern blot hybridization with a bovine papillomavirus type 2 probe. the molecule was cloned ...	1988	2824849
mutational analysis of the 3' open reading frames and the splice junction at nucleotide 3225 of bovine papillomavirus type 1.	functional analysis of the 3' open reading frames (orfs) of bovine papillomavirus type 1 (bpv-1) has been complicated by the organization of that part of the genome. a region between nucleotides (nt) 3173 and 3551 contains three overlapping orfs (e2, e3, and e4), as well as a 3' splice junction at nt 3225 which is used by many of the bpv-1 transcripts. to more clearly assign functions to specific orfs in this region, single-base substitution mutations were generated which introduced translationa ...	1987	2824822
human cytomegalovirus (hcmv) enhances bovine papilloma virus (bpv) transformation in vitro.	infection of nih 3t3 cells with a combination of hcmv and bpv resulted in more foci than infection with bpv alone. foci were microscopically apparent at 4 days in the mixed infection and did not appear until 2 days later in the cultures infected with bpv alone. the enhancement was abolished by heat inactivation of the hcmv and also when the hcmv was replaced by a "mock inoculum." southern blot analysis of cellular dna from transformed cells showed a similar amount of extrachromosomal bpv dna in ...	1987	2824682
the p39 promoter of minute virus of mice directs high levels of bovine growth hormone gene expression in the bovine papilloma virus shuttle vector.	the promoter of the capsid-coding genes of the autonomous parvovirus minute virus of mice (mvm) is shown to drive high levels of expression of the heterologous bovine growth hormone (bgh) gene in a bovine papilloma virus (bpv)-based shuttle vector. the expression of bgh directed by the mvm p39 promoter was, on average, higher than that obtained from the widely used metallothionein promoter. these results indicate that the mvm-p39/bpv shuttle vector will be generally useful for the high-level exp ...	1987	2824293
expression of human uterine tissue-type plasminogen activator in mouse cells using bpv vectors.	human tissue-type plasminogen activator (t-pa) cdna was cloned from uterine tissue and engineered in expression vectors for production in mouse c127 cells. the vectors consisted of the bovine papilloma virus-1 (bpv-1) genome and t-pa transcriptional unit with a mouse metallothionein (mt-1) promoter at the 5' end and mt-1 genomic sequences or sv40 early introns and polyadenylation signals at the 3' end. analysis of the expression vectors transfected into cells revealed that t-pa is expressed 100- ...	1987	2824147
stimulation of cellular dna synthesis by wild type and mutant bovine papillomavirus dna.	microinjection of recombinant plasmids containing bovine papillomavirus type 1 dna into the nuclei of mouse c127 cells results in the stimulation of cellular dna synthesis. mutations in the viral e2 gene have no apparent effect on this activity even though the same mutations prevent efficient c127 cell focus formation and inhibit transactivation by this gene.	1987	2823817
proteins present in bovine papillomavirus particles.	analysis by two-dimensional gel electrophoresis and silver staining of heavy full, light full, and empty bovine papillomavirus particles has shown that the major capsid protein l1 is highly modified. besides exhibiting at least 13 isoelectric point variants of approximately the same molecular mass (54 kilodaltons), it is suggested that an additional heavier protein chain (69 kilodaltons) is also derived from l1 by glycosylation. these modifications may stabilize the particle structure. treatment ...	1987	2822965
reindeer papillomavirus transforming properties correlate with a highly conserved e5 region.	a papillomavirus was isolated from the epithelial layer of a cutaneous fibropapilloma on a swedish reindeer (rangifer tarandus). reindeer papillomavirus (rpv) is morphologically indistinguishable from other papillomaviruses, but the restriction enzyme cleavage pattern of its genome is different. no sequence homology was detected between rpv dna and the dnas of bovine papillomavirus type 1 (bpv-1) and avian papillomavirus when hybridization was performed under stringent conditions. however, the r ...	1987	2822949
skin cancer and papillomaviruses in cattle.	we examined proliferative lesions on the sun-exposed, unpigmented skin of 13 cattle. ages of animals at first examination ranged from 4 to 15 years, and 4 were observed for from one to 3 years, during which time progression to malignancy occurred in 2 of them. early lesions consisted of keratin scales and horns; histology showed underlying acanthosis and hyperkeratosis. advanced lesions were either squamous cell carcinomas or basaloid tumours with sebaceous and/or squamous differentiation; some ...	1987	2822781
genetic and biochemical definition of the bovine papillomavirus e5 transforming protein.	mutations surrounding the first methionine codon of the e5 transforming gene of bovine papillomavirus (type 1) were analyzed for their effect on cellular transformation and on the synthesis of the 7-kd e5 polypeptide. frameshift mutations upstream of this methionine codon (bp 3879) affect neither transforming activity nor the ability to synthesize full-size e5 protein. in contrast, frameshift mutations distal to this position result in the inhibition of cell transformation and prevent synthesis ...	1987	2822390
optimizing gene expression in bpv-transformed cells: effects of cell type on enhancer/promoter interaction.	we have compared several combinations of enhancers and promoters in expressing the chloramphenicol acetyl transferase gene in transient assays, in mouse c127, the most widely used host cell for the bovine papilloma virus (bpv) expression vector. of the various combinations tested, the unit comprised of the sv40 enhancer and adenovirus type 2 major late promoter (mlp) was the most active in bpv transformed c127 cells. we further demonstrate that untransformed and bpv transformed c127 cells respon ...	1987	2821493
isolation and characterization of minichromosome particles that contain a glucocorticoid-modulated promoter.	a procedure for the enrichment of minichromosomes, composed of bovine papilloma virus and the long terminal repeat element of the mouse mammary tumor virus (mtv), from isolated nuclei is described. up to 60% of the minichromosomes were extracted as nucleoprotein particles. these particles sediment in sucrose gradients as 160s complexes. hormone-labeled glucocorticoid receptor co-purifies with these complexes in a specific fashion. between four and six molecules of receptor are bound per minichro ...	1987	2821487
mouse cell lines that use heat shock promoters to regulate the expression of tissue plasminogen activator.	the promoters from drosophila and human 70,000-dalton heat shock protein (hsp70) genes were linked to human tissue plasminogen activator (tpa) cdna. mouse c127 cells were transformed with bovine papilloma virus (bpv) vectors carrying the hybrid hsp70/tpa genes. stable bpv-transformed cell lines were selected and analyzed for tpa expression before and after heat shock. in most cell lines, there was a low level of tpa production even in the absence of heat shock or other obvious stress. after heat ...	1987	2820678
promoting activity of betel quid ingredients and their inhibition by retinol.	ingredients of betel quids, which have been linked to the high incidence of precancerous oral lesions and oral cancers, were examined for their promoting activity. aqueous extracts were tested using the bovine papillomavirus (bpv) dna transformation assay, which consists of cultured c3h/10t1/2 cells transfected with the plasmid pdpbv-1 as targets, and the frequency of transformed foci as endpoints. areca nut extracts enhanced the formation of bpv dna-induced transformed foci approximately tenfol ...	1989	2713825
structure and expression of two human metallothionein-i isoform genes and a related pseudogene.	three members of the human metallothionein-i gene family have been cloned and characterized. two of the genes encode closely related but distinct metallothionein-i subtypes. both of these genes are functional as shown by their transcription in cultured hepatoblastoma cells and by their ability to render transfected cells resistant to cadmium toxicity. the cotranscription of these nonallelic genes shows that the previously observed microheterogeneity of metallothionein-i protein preparations is d ...	1985	2581970
tumorigenic latency and separable stages during fibrosarcoma development in transgenic mice carrying papillomavirus genomes.	transgenic mice have been established carrying the genomes of bovine papillomavirus type 1 (bpv-1), and human papillomaviruses types 5 and 18. transcriptional dormancy is characteristic of all three viral genomes in transgenic mouse lines maintained for 2-4 years. only bpv-1, which induces both dermal and epidermal pathology in its natural host, has been found to elicit abnormalities when carried in transgenic mice. the bpv-1 genome acts in these mice as a tissue specific oncogene, in that it el ...	1989	2562186
bovine papillomavirus type i induces resistance to ca+(+)-induced terminal differentiation in murine keratinocytes.	bovine papillomavirus type 1 (bpv-1) was expressed in established mouse balb/mk epidermal keratinocytes. in each of the transfected cell lines, dna synthesis was stimulated by epidermal growth factor (egf) and inhibited by type beta transforming growth factor to an extent similar to that in parental cells. in contrast, the bpv-1-transfectants were resistant to the induction of terminal differentiation by extracellular ca(+)+. first, bpv transfectants continued to respond to egf in the presence o ...	1989	2561735
[using bpv transforming foci as selective markers to express hbsag].	we constructed a plasmid pbmthbr2 containing mouse mt promoter, entire hbsag gene (pres and s gene), splicing signal from sv40 and complete bpv genome. using calcium phosphate precipitation technique to transform c127 cells and using bpv transforming foci as selective markers, we obtained transformed cell clones. the experiment shows that 57% of the cloned cell lines can secrete hbsag continuously.	1989	2561512
injection of xenopus eggs before activation, achieved by control of extracellular factors, improves plasmid dna replication after activation.	injection of molecular probes into unfertilized xenopus eggs requires suppression of activation. but the unfertilized egg is poised for activity, and pricking, like sperm penetration, triggers the start of the first cell cycle. methods of suppressing activation generally rely on introduction of drugs into the cell, but some of these techniques are irreversible. i report here that injection without activation can also be accomplished by simply limiting extracellular free ca2+ to 1-2 microm. the s ...	1989	2559091
complex formation of human papillomavirus e7 proteins with the retinoblastoma tumor suppressor gene product.	the e7 proteins encoded by the human papillomaviruses (hpvs) associated with anogenital lesions share significant amino acid sequence homology. the e7 proteins of these different hpvs were assessed for their ability to form complexes with the retinoblastoma tumor suppressor gene product (p105-rb). similar to the e7 protein of hpv-16, the e7 proteins of hpv-18, hbv-6b and hpv-11 were found to associate with p105-rb in vitro. the e7 proteins of hpv types associated with a high risk of malignant pr ...	1989	2556261
purification and dna-binding properties of human papillomavirus type 16 e6 protein expressed in escherichia coli.	unfused human papillomavirus type 16 (hpv 16) e6 protein was expressed in escherichia coli using a lambda pl promoter system. the protein was isolated from the cells as inclusion bodies, extracted by 6 m guanidine-hcl, and purified by chromatography. the purified protein had high affinity to dna and was demonstrated for the first time to bind to a specific sequence within the long control region of hpv 16.	1989	2556128
genetic evidence that acute morphologic transformation, induction of cellular dna synthesis, and focus formation are mediated by a single activity of the bovine papillomavirus e5 protein.	the bovine papillomavirus (bpv) type 1 e5 gene encodes a 44-amino-acid protein that can stably transform cultured rodent cells when expressed in the absence of all other viral genes. we have previously constructed a bpv-simian virus 40 recombinant virus (pava-1) which efficiently expresses the bpv type 1 e5 gene in infected cells (j. settleman and d. dimaio, proc. natl. acad. sci. usa 85:9007-9011, 1988). within 48 h of pava-1 infection, the vast majority of mouse c127 cells underwent a dramatic ...	1989	2555701
phosphorylation sites of the e2 transcriptional regulatory proteins of bovine papillomavirus type 1.	the e2 open reading frame of bovine papillomavirus type 1 (bpv-1) encodes three transcriptional regulatory proteins. the full-length open reading frame encodes a protein of 410 amino acids which functions as a transcriptional transactivator. two transcriptional repressor proteins, e2-tr and e8/e2, contain the c-terminal 249 and 204 amino acids, respectively. we have expressed both the full-length e2 protein and the e2-tr repressor protein in insect cells, by using recombinant baculoviruses, and ...	1989	2555544
inducible expression of encephalomyocarditis virus 3c protease activity in stably transformed mouse cell lines.	an inducible expression vector system has been developed to facilitate the study of the effects of individual virus gene products on cell function. the vector utilizes the mouse metallothionein promoter carried on the bovine papillomavirus genome. conditions which optimize the induced expression of open reading frames inserted downstream from the mouse metallothionein promoter have recently been described. in this communication we describe the use of this system to clone and express the encephal ...	1989	2555538
suppression of focus formation by bovine papillomavirus-transformed cells by contact with non-transformed cells: involvement of sugar(s) and phosphorylation.	focus formation by bovine papilloma virus-transformed c127 cells was inhibited by direct contact with non-transformed c127 cells. the suppressive capacity of c127 cells was abolished by introduction of the neomycin resistance gene (neor) but not by that of the hygromycin resistance gene (hygrr). though both genes code for phosphotransferase which inactivates the aminoglycoside antibiotics, their substrates are different, i.e., there is no cross-resistance between them. as the neomycin phosphotra ...	1989	2555308
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 ...	1989	2554558
the e2 trans-activating protein of bovine papillomavirus type 1 (bpv1) is serine-phosphorylated in vivo.	the e2 open reading frame of bovine papillomavirus 1 (bpv1) encodes both positive and negative transcriptional regulatory factors. the full-length e2 gene polypeptide is a strong transcriptional transactivator that acts on enhancers within the papillomavirus long control region (lcr), and two shorter e2 proteins function as transcription repressors. a vaccinia recombinant virus harboring the full length e2 coding sequence of bpv1 directs the synthesis of a 48 kd phosphoprotein with specific dna ...	1989	2554235
nutritional requirements of papillomavirus-transformed mouse cells and an uninfected parent line in serum-free culture.	a serum-free culture system was used to compare the nutritional requirements of mouse mammary cells transformed by bovine papillomavirus type 1 (id13 cells) and the uninfected parent line (c127 cells). the serum-free, chemically defined medium used for this study was an mcdb 151-based medium (mcdb 151+s+i), supplemented with epidermal growth factor, transferrin, hydrocortisone, ethanolamine, phosphoethanolamine, retinoic acid, trace metals, and insulin. proliferation of either cell type in serum ...	1989	2553658
mutational analysis of bovine papillomavirus type 1 e5 peptide domains involved in induction of cellular dna synthesis.	early gene e5 of bovine papillomavirus type 1 encodes a 44-amino-acid protein whose expression can transform immortalized mouse cell lines. we have previously reported that a chemically synthesized e5 peptide functions to induce cellular dna synthesis upon microinjection into growth-arrested mouse cells. we further defined the two e5 domains essential for the full dna synthesis induction activity by the analysis of e5 deletion and amino acid substitution mutant peptides. the first domain is the ...	1989	2552177
transforming activity of a 16-amino-acid segment of the bovine papillomavirus e5 protein linked to random sequences of hydrophobic amino acids.	the 44-amino-acid e5 protein of bovine papillomavirus type 1 is the smallest transforming protein yet described. previous results from our laboratory indicate that a hydrophobic core and specific carboxyl-terminal amino acids are required for the e5 protein to exert its transforming function. in this study, additional substitution mutations were generated in the e5 gene to determine the minimal amino acid sequence requirements for focus formation in mouse c127 cells. in most cases examined, subs ...	1989	2552136
structure, activity, and regulation of the bovine papillomavirus e5 gene and its transforming protein product.		1989	2551579
the bovine papillomavirus e5 transforming protein can stimulate the transforming activity of egf and csf-1 receptors.	the bovine papillomavirus e5 transforming gene encodes a 44 amino acid protein product that is localized to cytoplasmic membranes, including the plasma membrane. we now report that e5 can cooperate with human egf receptors and with human csf-1 receptors to induce cellular transformation of nih 3t3 cells. cooperation occurred in the absence of receptor stimulation by ligand, and it was further augmented by treatment with ligand. cooperation was not seen between e5 and either c-fes or c-src. the c ...	1989	2551505
independent glucocorticoid induction and repression of two contiguous responsive genes.	specific dna sequence elements which contain binding sites for the glucocorticoid receptor mediate the action of glucocorticoid hormones on gene transcription. in glucocorticoid-inducible genes, these glucocorticoid-responsive elements behave as hormone-inducible enhancers of transcription. we have taken advantage of the bovine papillomavirus (bpv) system to test the stringency of glucocorticoid regulation of transcription. bpv episomes were constructed to contain two hormone-regulated transcrip ...	1989	2550796
trans activation by the bovine papillomavirus e2 protein in saccharomyces cerevisiae.	the papillomavirus e2 protein functions as an enhancer-binding factor to promote transcription in mammalian cells. we found that one copy of the e2 binding site acted as an e2 protein-dependent upstream activating sequence in saccharomyces cerevisiae. additional copies of the binding motif further augmented transcription. these results imply that the e2 protein functionally interacts with highly conserved transcriptional elements.	1989	2550673
animal virus dna replication.		1989	2549858
amplification of bovine papillomavirus dna by n-methyl-n'-nitro-n-nitrosoguanidine, ultraviolet irradiation, or infection with herpes simplex virus.	treatment with n-methyl-n'-nitro-n-nitrosoguanidine (mnng) or irradiation with ultraviolet light (uv254 nm) induces amplification of integrated as well as episomal sequences of bovine papillomavirus (bpv) type 1 dna in bpv-1-transformed mouse c127 cells (i.e., id13 cells). this is shown by filter in situ hybridization and southern blot analysis of cellular dna. similarly, infection of id13 cells with herpes simplex virus (hsv) type 1 which has been shown to be mutagenic for host cell dna leads t ...	1989	2549724
the adeno-associated virus rep78 gene inhibits cellular transformation induced by bovine papillomavirus.	adeno-associated virus type 2 (aav) is a helper dependent parvovirus which can inhibit the oncogenic and transforming potential of its helper viruses: adenoviruses (ad) and herpesviruses. here we have assayed aav's ability to inhibit cellular transformation induced by bovine papillomavirus type 1 (bpv-1), a member of another family of dna viruses. aav was able to markedly inhibit bpv-1-induced transformation of contact-inhibited murine fibroblasts either by infection with virus particles or by d ...	1989	2549714
papillomavirus-associated inductions of cellular proteins in mouse c127 cells: correlation with the presence of open reading frame e2.	bovine papillomavirus type 1 (bpv-1) readily transforms mouse c127 cells, conferring the ability to grow in soft agar and to form tumors in athymic (nu/nu) mice. electrophoresis of total cellular proteins from these bpv-transformed lines on ultra-high resolution, giant two-dimensional gels displays the presence of novel, papillomavirus-related protein phenotypes. analysis of the established bpv-1-transformed c127 cell lines, id13 and id14, reveals a set of six proteins which are either absent or ...	1989	2549708
bovine papilloma virus encoded e2 protein activates lymphokine genes through dna elements, distinct from the consensus motif, in the long control region of its own genome.	activation of t cells by antigen, lectin or a combination of phorbol ester (pma) and calcium ionophore (a23187) leads to the induction of a set of lymphokine genes. transfection of a human t cell leukemia cell line, jurkat, or an african green monkey kidney cell line, cv1, with a cdna encoding e2 protein, a trans-activator of bovine papilloma virus type 1, results in activation of interleukin 2 (il-2), interleukin 3 (il-3) and granulocyte/macrophage colony-stimulating factor (gm-csf) genes in a ...	1989	2548843
stably expressed fipv peplomer protein induces cell fusion and elicits neutralizing antibodies in mice.	we have established bovine papilloma virus (bpv)-transformed mouse c127 cell lines that synthesize the peplomer protein of the feline infectious peritonitis virus (fipv) strain 79-1146. for this purpose, a new cassette expression vector phsl, which carries the drosophila hsp70 promotor and the polyadenylation signal of the moloney murine leukemia virus long terminal repeat, was constructed. cocultivation of the bpv-transformed cell lines with fipv-permissive feline fcwf-d cells resulted in polyk ...	1989	2548329
dual loci of dna bending in the bovine papillomavirus upstream regulatory region.	recombinant clones containing all or portions of the bovine papillomavirus (bpv) upstream regulatory region (urr) were constructed. when analyzed by polyacrylamide gel electrophoresis, the cloned urr sequences exhibited electrophoretic properties characteristic of dna containing bend sites. two distinct bend centers were identified, mapping to approximately 7477 and 7790 respectively on the bpv genome. no other loci of static dna bending were detected in the urr region of the bpv genome.	1989	2546330
transcriptional termination between bovine papillomavirus type 1 (bpv-1) early and late polyadenylation sites blocks late transcription in bpv-1-transformed cells.	bovine papillomavirus type 1 (bpv-1) is a small dna tumor virus which induces fibropapillomas in cattle and transforms rodent cells in culture. transcripts are derived from a single strand of the circular viral genome, which has multiple promoters and two polyadenylation sites. in the transformed cell, the first (early) polyadenylation site is utilized exclusively and, therefore, only the early region is expressed. transcription of the late genes, which requires use of the second (late) polyaden ...	1989	2545923
infectious papillomavirus in the vapor of warts treated with carbon dioxide laser or electrocoagulation: detection and protection.	papillomavirus dna has been reported recently in the vapor (smoke plume) derived from warts treated with carbon dioxide laser; this raises concerns for operator safety. we therefore have studied a group of human and bovine warts to define further the potential risk of wart therapy and to test whether a surgical mask could reduce exposure. half of each wart was treated with carbon dioxide laser and the other half with electrocoagulation. the vapor produced by each form of therapy was collected wi ...	1989	2545749
identification and characterization of the bpv-2 l2 protein.	the bovine papilloma virus type 2 (bpv-2) l2 open reading frame was cloned into a lambda pl promoter expression vector. this plasmid was shown to express a fusion protein which constituted 75% of the bpv-2 l2 orf linked to the first 13 n-terminal amino acids of the lambda cll gene product. antisera generated against this fusion protein were used to identify the l2 gene product as a 64,000-da protein in bpv-2 virions. western blot analysis demonstrated that the l2 viral protein was present in ful ...	1989	2545035
specific chromosomal abnormalities characterize fibrosarcomas of bovine papillomavirus type 1 transgenic mice.	in the bpv1.69 line of transgenic mice, the bovine papillomavirus type 1 genome elicits both benign dermal fibroblastic proliferation (fibromatoses) and malignant fibrosarcomas. because these lesions arise only with time, nonviral factors appear to be involved. we have karyotyped several primary tumors as well as a series of low-passage cell lines derived both from fibromatoses and from fibrosarcomas. the fibrosarcomas, but not the preneoplastic fibromatoses, show consistent abnormalities of one ...	1989	2544888
characterization of bovine papillomavirus type 1-transformed clones which show distinct transformed phenotypes.	seventeen independent cell clones were isolated from c127 cells transformed by bovine papillomavirus type 1 (bpv-1). transformants showed differing degrees of expression of the transformed phenotype as monitored by saturation density, doubling time, growth in medium with a low serum concentration and colony-forming efficiency in soft agar. the degree of expression of the transformed phenotype did not correlate with either the bpv-1 copy number or levels of bpv-1-specific rna in the transformed c ...	1989	2543792
the effect of bovine herpesvirus type 1 glycoproteins gi and giii on herpesvirus infections.	we expressed the bovine herpesvirus type 1 (bhv-1) glycoproteins, gi and giii, in bovine cells using a bovine papillomavirus vector. the proteins expressed by these cells had the same mr as the native bhv-1 proteins and monoclonal antibodies detected no differences in their antigenic structure. cells expressing gi were infected with either bhv-1 or herpes simplex virus type 1 (hsv-1). the number of plaques in gi-expressing cells was similar to that seen with normal fibroblasts infected with bhv- ...	1989	2543789
expression of epstein-barr virus membrane antigen gp340/220 in mouse fibroblasts using a bovine papillomavirus vector.	epstein-barr virus (ebv) membrane antigen glycoproteins gp340 and gp220 are encoded by a single gene. we have inserted this gene into a bovine papillomavirus (bpv) vector and expressed gp340/220 in mammalian cells under the control of the mouse metallothionein promoter. the proteins produced were of similar mr, showed similar antigenic specificity and were transported to the same subcellular location as the authentic gp340/220. the inclusion of heavy metal ions in the medium had no effect on the ...	1989	2543757
multiple cooperative interactions constrain bpv-1 e2 dependent activation of transcription.	transcription directed by the bpv-1 long control region (lcr) is conditional upon activation by the virally encoded e2 protein. within the 1.0 kb lcr there are five separate regions, a to e, that contain e2 responsive enhancers. the smallest functional region, a, is only 38 bp and contains two copies of the consensus sequence acc(n)6ggt that is known to function as an e2 binding site in vitro. we show that a pair of these constitutes a minimal functional e2 responsive enhancer element but that t ...	1989	2542891
cell-heritable stages of tumor progression in transgenic mice harboring the bovine papillomavirus type 1 genome.	tumorigenesis of dermal fibroblasts in a line of transgenic mice carrying the bpv-1 genome was found to involve distinct proliferative stages. cell cultures derived from normal skin, from benign proliferative fibromatoses, and from malignant fibrosarcomas each evidenced distinguishable, cell-heritable characteristics. the latent viral genome was transcriptionally inactive in normal-appearing skin and was activated in the dermal fibromatoses. fibrosarcoma cells grew continuously in culture, forme ...	1989	2542769
genetic assignment of multiple e2 gene products in bovine papillomavirus-transformed cells.	the e2 open reading frame of bovine papillomavirus type 1 has been shown genetically to encode at least three transcriptional regulatory factors, and three e2 specific proteins have been recently identified in virally transformed rodent cells. in this study, the genes encoding these e2 specific proteins have been determined. the 48-kilodalton (kda) protein was identified as the product of a full-length e2 open reading frame cdna, which confirmed that this polypeptide is the e2 transactivator. th ...	1989	2542621
specific recognition nucleotides and their dna context determine the affinity of e2 protein for 17 binding sites in the bpv-1 genome.	the dna context of nucleotides that a protein recognizes can influence the strength of the protein-dna interaction. moreover, in prokaryotes, understanding the quantitative differences in binding affinities that result in part from the dna context is often important in describing regulatory mechanisms. nevertheless, these issues have not been a major focus yet for the investigation of protein-dna interactions in eukaryotes. in this study, we explored the binding specificity and the range of affi ...	1989	2542129
expression of hepatitis b virus surface antigen containing the pre-s region in mammalian cell culture system.	the surface antigen of hepatitis b virus (hbv) has been expressed in a mouse cell line using metallothionein-bovine papilloma virus vectors. four different recombinant plasmids were used and it was found that the expression level varies significantly from one plasmid to another. removing the hbv polyadenylation signal from the plasmid drastically reduced the expression level. providing even a heterologous polyadenylation signal improved the expression level from the reduced one by at least tenfo ...	1989	2541576
the e5 oncoprotein of bovine papillomavirus is oriented asymmetrically in golgi and plasma membranes.	the e5 oncoprotein of bpv-1 is a 44 amino acid, hydrophobic polypeptide which is present in membrane fractions of transformed cell homogenates. to define the specific cellular membrane compartments with which e5 associates, immunofluorescence and immunoelectron microscopy were performed using an affinity-purified antibody specific for the e5 carboxyl-terminus. two cell systems which overexpressed the e5 protein were analyzed: (1) balb/c 3t3 mouse cells transformed by a bpv-1 cdna expressing the ...	1989	2541554
genetic analysis of crpv pathogenesis: the l1 open reading frame is dispensable for cellular transformation but is required for papilloma formation.	genetic studies to elucidate the role of papillomaviruses in the development and progression of tumors have been severely hampered because the viruses cannot be grown in tissue culture and therefore mutants are not available. we have employed recombinant dna for papilloma induction to identify essential sequences involved in papillomavirus pathogenesis. here, we demonstrated that deleting most of the open reading frame (orf) l2 did not affect the potential of viral cottontail rabbit papillomavir ...	1989	2541552
successive steps in the process of immortalization identified by transfer of separate bovine papillomavirus genes into rat fibroblasts.	transfer of neor and bovine papillomavirus type 1 (bpv1) dna into rat embryo fibroblasts led to colony formation in g418-containing medium, with no detectable background in controls with neor dna alone. more than 50% of the drug-resistant clones could be further propagated in culture. the genetic functions of bpv1 involved in colony formation and in long-term immortalization were investigated by both translation termination mutations in the full-length genome, which inactivate individual open re ...	1989	2541438
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 ...	1989	2541389
transcriptional regulation by estrogen of episomal prolactin gene regulatory elements.	as a first step in defining the role of chromatin structure in steroid-regulated gene transcription, we have established a steroid-responsive minichromosome system that contains the 5' upstream regulatory region of the rat prl gene (prl) from -10 to -1960-basepairs fused to the antibiotic resistance gene, tn5. the hybrid gene was inserted into a bovine papilloma virus (bpv) vector and then transfected into gh3 cells. southern analysis of total genomic dna revealed that the prl-tn5-bpv dna existe ...	1989	2540428
selective enhancement of bovine papillomavirus type 1 dna replication in xenopus laevis eggs by the e6 gene product.	genetic analyses of bovine papillomavirus type 1 (bpv-1) dna in transformed mammalian cells have indicated that the e6 gene product is essential for the establishment and maintenance of a high plasmid copy number. in order to analyze the direct effect of the e6 protein on the replication of a bpv-1-derived plasmid, a cdna containing the bpv-1 e6 open reading frame was subcloned into an sp6 vector for the in vitro synthesis of the corresponding mrna. the sp6 e6 mrna was injected into xenopus laev ...	1989	2540419
efficient activation of transcription in yeast by the bpv1 e2 protein.	the full-length gene product encoded by the e2 open reading frame (orf) of bovine papillomavirus type 1 (bpv1) is a transcriptional transactivator. it is believed to mediate its effect on the bpv1 long control region (lcr) by binding to motifs with the consensus sequence accn6ggt. the minimal functional cis active site, called the e2 response element (e2re), in mammalian cells comprises two copies of this motif. here we have shown that e2 can function in saccharomyces cerevisiae by placing an e2 ...	1989	2539584
mutational analysis of bovine papillomavirus e6 gene.	the bovine papillomavirus e6 gene can independently transform mouse c127 cells. to characterize e6 in greater detail, we created 16 site-directed mutations in e6, including substitution mutations in the cysteine codons of the four cys-x-x-cys motifs that are conserved in all papillomavirus e6 proteins. proteins mutated in six of the seven cysteines tested, as well as those lacking the nonconserved c-terminus, were stable in transfected cells but were unable to induce morphological transformation ...	1989	2539522
loss of bovine papillomavirus dna replication control in growth-arrested transformed cells.	the bovine papillomavirus type 1 (bpv-1) genome replicates as a plasmid within the nuclei of bpv-1-transformed murine c127 cells at a constant multiple copy number, and spontaneous amplification of the viral dna is rarely observed. we report here that a mutant bpv-1 plasmid within a contact-inhibited c127 cell line replicated as a stable multicopy plasmid in exponentially growing cells but amplified to a high level in confluent cell culture. in situ hybridization analysis revealed that most of t ...	1989	2539513
evidence for multiple vegetative dna replication origins and alternative replication mechanisms of bovine papillomavirus type 1.	by following up the chance detection in the electron microscope of a dna replication intermediate within a preparation of bovine papillomavirus (bpv-1) dna isolated from purified virus particles, information was obtained about the mechanism of bpv-1 genome replication during the final stages of virus multiplication in naturally infected bovine wart tissue. the structure of viral replication intermediates was investigated by electron microscopic analysis of viral dna linearized by digestion with ...	1989	2539483
identification of bovine papillomavirus e1 mutants with increased transforming and transcriptional activity.	the e1 open reading frame of bovine papillomavirus type 1 (bpv) has been shown previously to encode trans-acting functions, m and r, that are involved in extrachromosomal replication of the viral genome. we have determined that several e1 mutants mapping in both the m and r regions and a single mutant of the upstream regulatory region have a higher transforming activity on mouse c127 cells than the wild-type genome does. a representative mutant in m, a mutant in r, and the upstream regulatory re ...	1989	2538656
bovine papillomavirus type 1 encodes two forms of a transcriptional repressor: structural and functional analysis of new viral cdnas.	genetic and biochemical evidence has established that the e2 open reading frame (orf) of bovine papillomavirus type 1 encodes at least two different site-specific dna-binding proteins, one which activates and the other which represses expression from a viral promoter (p. f. lambert, b. a. spalholz, and p. m. howley, cell 50:69-78, 1987). we have obtained data which show that a second form of the repressor gene is expressed in transformed cells harboring stable viral plasmids. the structural deta ...	1989	2538655
the bovine papillomavirus type 1 transcriptional activator e2 protein binds to its dna recognition sequence as a dimer.	the transcriptional trans-activator e2 protein from bovine papillomavirus type 1 has been shown to bind to the dna consensus sequence accn6ggt. we have produced the dna-binding domain of the e2 protein as a recombinant protein in escherichia coli. the e2 dna-binding domain was purified as two different molecular weight forms. using these purified proteins, we show that two molecules of the e2 protein bind to a single dna consensus binding site.	1989	2538035
papillomavirus polypeptides e6 and e7 are zinc-binding proteins.	papillomavirus proteins e6 and e7 have cys-x-x-cys repeats which have been suggested to mediate zinc binding. we have developed a modification of an assay that detects zinc binding to proteins immobilized on filters. using well-characterized metalloproteins, we show that, under reducing conditions, this assay distinguishes proteins that coordinate zinc through cysteine residues from those that bind the metal through other amino acids. under these conditions, e6 and e7 polypeptides of human papil ...	1989	2536841
e2 polypeptides encoded by bovine papillomavirus type 1 form dimers through the common carboxyl-terminal domain: transactivation is mediated by the conserved amino-terminal domain.	the e2 open reading frame (orf) of bovine papillomavirus type 1 (bpv-1) encodes positive- and negative-acting factors that regulate viral gene expression. the full-length orf encodes a transactivator, and two transcriptional repressors are expressed from the 3' half of the orf. previous analysis has shown that a conserved c-terminal region of 101 amino acids, which is shared by e2 transactivator and repressor proteins, contains the specific dna binding activity. further analysis of the e2 transa ...	1989	2536165
complete nucleotide sequence of the chromosomal gene for human il-4 and its expression.	we have isolated a chromosomal dna segment of the human il-4 gene based on homology with a human il-4 cdna sequence and determined its complete nucleotide sequence. the human il-4 gene, which occurs as a single copy in the haploid genome, is mapped on chromosome 5. it is composed of four exons and three introns and is approximately 10 kilobase pairs in size. 5'-flanking regions of human and mouse il-4 genes share about 85% homology extending more than 500 base pairs upstream of a "tata" like seq ...	1989	2535858
open reading frames e6 and e7 of bovine papillomavirus type 1 are both required for full transformation of mouse c127 cells.	a series of mutations in open reading frames (orfs) e6 and e7 of bovine papillomavirus type 1 (bpv1) was constructed to analyze the roles of these orfs in transformation of mouse c127 cells. the mutations were designed to prevent synthesis of specific proteins encoded by these genes. none of the mutations caused a decrease in the focus-forming activity of the full-length viral genome or in the ability of the viral dna to replicate as a high-copy-number plasmid. analysis of these mutants in the a ...	1989	2535732
tumorigenicity, invasiveness and metastatic capability of fr3t3 rat cells before and after transfection with bovine papilloma virus type 1 dna.	fischer rat fr3t3 cells were tested for tumorigenicity, invasive and metastatic capabilities before and after transfection, either with the entire bovine papilloma virus type 1 (bpv-1) genome or with a plasmid (pv69) containing a 69 per cent bam h1-hind iii fragment of the bpv-1 genome as well as bacterial sequences. cell lines were grouped as parental, pv69-transfectants, bpv-1 transfectants, in vitro derivatives, and in vivo derivatives. the tumorigenic, invasive and metastatic capabilities of ...	1989	2535681
the human papillomavirus type 18 (hpv18) e2 gene product is a repressor of the hpv18 regulatory region in human keratinocytes.	the human papillomavirus type 18 (hpv18) long control region (lcr) harbors transcriptional promoter and enhancer elements. recombinant plasmids bearing all or part of the hpv18 lcr cloned in enhancer or promoter configuration upstream of the chloramphenicol acetyltransferase (cat) gene were transfected into human fibroblasts and keratinocytes. although the hpv18 enhancer can function in the absence of e2 gene products in both fibroblasts and keratinocytes, the promoter activity of the hpv18 lcr ...	1989	2476572
identification of l2 open reading frame gene products of bovine papillomavirus type 1 using monoclonal antibodies.	four hybridoma cell lines producing monoclonal antibodies (mabs) to bovine papillomavirus type 1 (bpv-1) l2 open reading frame (orf) gene products have been established from mice immunized with a bpv-1 l2-beta-galactosidase fusion protein. hybridomas were selected and cloned (from over 700 hybridomas) on the basis of specific reactivity of supernatant fluids with bpv-1 l2 epitopes on disrupted bpv-1 particles and l2-beta-galactosidase fusion proteins by elisa and western blotting, and with aceto ...	1989	2471804
expression in escherichia coli of seven dna fragments comprising the complete l1 and l2 open reading frames of human papillomavirus type 6b and localization of the 'common antigen' region.	molecular cloning was used to express human papillomavirus type 6b (hpv-6b) antigens in escherichia coli. seven genomic dna fragments of hpv-6b which together comprise the complete l1 and l2 open reading frames, known to code for capsid proteins, were cloned and expressed in e. coli as both beta-galactosidase and trpe fusion proteins. western blots of hpv-6b beta-galactosidase fusion proteins using 'genus-specific' antisera produced by immunization of rabbits with disrupted bovine papillomavirus ...	1989	2471790
demonstration of in vitro synthesis of human papilloma viral proteins from hand and foot warts.	hpv particles purified from [35s]-methionine labeled and unlabeled halves of single hand and foot warts have been fractionated into empty, light full, and heavy full particles by buoyant density gradient centrifugation, and their proteins analyzed by two-dimensional gel electrophoresis (ief and nephge) and visualized by either fluorography or silver staining. the l1 coat protein (54 kd) was found in trace amounts in unmodified and slightly modified forms in the labeled empty and light full parti ...	1989	2470829
human antibodies react with an epitope of the human papillomavirus type 6b l1 open reading frame which is distinct from the type-common epitope.	recombinant proteins encoded by the human papillomavirus type 6b (hpv6b) l1 open reading frame react with sera from patients with condylomata acuminata and also react with rabbit antiserum raised against sodium dodecyl sulfate-disrupted bovine papillomavirus type 1 (bpv1) virions. to map the immunoreactive epitopes, a series of procaryotic expression plasmids was made which contained a nested set of 3' to 5' deletions in the hpv6b l1 open reading frame. the deleted plasmids expressed a set of ca ...	1989	2463384
a transfected alpha-casein minigene bypasses posttranscriptional control by hormones, but retains cell-substratum regulation in mammary epithelial cells.	dna-mediated gene transfection using an alpha-casein minigene cloned into a bovine papilloma virus (bpv)-based neomycin-selectable expression vector has been employed to study the mechanisms by which hormonal and cell-substratum interactions regulate milk protein gene expression. permanently transformed clones and pooled populations of normal midpregnant mouse mammary epithelial cells (comma-d) containing the minigene express an authentic rat alpha-casein mrna, as well as a series of larger cyto ...	1988	2458523
enhanced production of hepatitis b virus surface antigen in mouse c127 cell on a bovine papillomavirus-metallothionein vector.	we have constructed a recombinant plasmid pcps12 containing the hepatitis b viral surface antigen (hbsag) gene linked to the mouse metallothionein promoter on a bpv-pml2 vector. two stable clones s12-8 and s12-2, obtained by transfection of the mouse c127 cells with pcps12 propagated in dam+ dcm+ and dam- dcm- escherichia coli respectively, exhibited different types of response to 5-azacytidine (5-aza-cr) and cadmium (cd) induction. in s12-8, the productivity of hbsag was enhanced by 5-aza-cr or ...	1988	2451524
transcriptional regulation of the human papillomavirus-16 e6-e7 promoter by a keratinocyte-dependent enhancer, and by viral e2 trans-activator and repressor gene products: implications for cervical carcinogenesis.	the transcriptional promoter of the candidate e6-e7 transforming gene region of human papillomavirus (hpv)-16 (p97) was active in transiently transfected cervical carcinoma cells when linked to the hsv-1 tk or bacterial cat genes. sequences 5' to p97 contain a short enhancer element responding to cellular factor(s) in uninfected human foreskin keratinocytes and in cervical carcinoma cells, but not in human or animal fibroblasts. the e2 trans-activator products of hpv-16 or of the related bovine ...	1987	2448139
stable expression of recombinant factor viii molecules using a bovine papillomavirus vector.	the bleeding disorder in hemophilia a results from a deficiency or abnormality of factor viii (fviii), a member of the coagulation cascade. fviii is a large glycoprotein (approximately 350,000 daltons) that is activated by a series of proteolytic cleavages. during activation, a large internal domain (b domain) is removed, resulting in an active complex comprised of the amino and carboxyl subunits of the parental molecule. using a bovine papillomavirus expression vector system, we have establishe ...	1987	2448100
topographical and conformational epitopes of bovine papillomavirus type 1 defined by monoclonal antibodies.	monoclonal antibodies (mabs) were generated against sodium dodecyl sulfate-disrupted bovine papillomavirus type 1 (bpv-1). when screened by enzyme-linked immunosorbent assay (elisa) on intact and disrupted bpv-1, -2, and deer papillomavirus, three patterns of reactivity were defined: reactivity only with intact virus, with both intact and disrupted virus, and only with disrupted virus. on the basis of elisa results, the topographical location and requirement for conformation for immunoreactivity ...	1987	2446044