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[influence of age in the prevalence of high-risk human papiloma virus in women with pre-neoplasic cervical lesions in navarra, spain].cervical carcinoma (cc) is the second cause of death among women aged 15 and 44 in spain. cc is linked to hig-risk human papillomavirus (hr-hpv) infection and its prevalence varies according age and geographical region. the awereness of the latter is essential for public health prevention efforts. the aim was to study the age related in hr-hpv genotypes in cytologies with squamous intraepithelial lesion (sil).201728181989
phylogenetic and functional analysis of sequence variation of human papillomavirus type 31 e6 and e7 oncoproteins.high-risk human papillomaviruses (hpv) are the causative agents of cervical and other anogenital cancers as well as a subset of head and neck cancers. the e6 and e7 oncoproteins of hpv contribute to oncogenesis by associating with the tumour suppressor protein p53 and prb, respectively. for hpv types 16 and 18, intratypic sequence variation was shown to have biological and clinical significance. the functional significance of sequence variation among hpv 31 variants was studied less intensively. ...201627197052
cloning and expression of l1 protein human papillomavirus type 31 isolated from iranian patients in escherichia coli.human papillomavirus (hpv), a major pathogen of human cervical cancer, contains a full-length l1 gene encoding its surface capsid protein. one group of potential vaccine candidates against this virus in iranian patients is based on surface protein components such as hpv31 l1 protein that can make virus-like particles (vlps). the high immunity response stimulation of this effecter vlp was observed in host, suggesting that the individual characteristics of a particular effecter may require empiric ...201627244269
impact of human papillomavirus (hpv) 16 and 18 vaccination on prevalent infections and rates of cervical lesions after excisional treatment.human papillomavirus vaccines prevent human papillomavirus infection and cervical precancers. the impact of vaccinating women with a current infection or after treatment for an human papillomavirus-associated lesion is not fully understood.201626892991
homologous recombination repair factors rad51 and brca1 are necessary for productive replication of human papillomavirus 31.high-risk human papillomavirus 31 (hpv31)-positive cells exhibit constitutive activation of the atm-dependent dna damage response (ddr), which is necessary for productive viral replication. in response to dna double-strand breaks (dsbs), atm activation leads to dna repair through homologous recombination (hr), which requires the principal recombinase protein rad51, as well as brca1. previous studies from our lab demonstrated that rad51 and brca1 are expressed at high levels in hpv31-positive cel ...201526699641
interferon kappa inhibits human papillomavirus 31 transcription by inducing sp100 proteins.high-risk human papillomaviruses (hr-hpv) establish persistent infections in keratinocytes, which can lead to cancer of the anogenital tract. interferons (ifns) are a family of secreted cytokines that induce ifn-stimulated genes (isgs), many of which display antiviral activities. transcriptome studies have indicated that established hr-hpv-positive cell lines display a reduced expression of isgs, which correlates with decreased levels of interferon kappa (ifn-κ), a type i ifn constitutively expr ...201526491169
association of human papillomavirus 31 dna load with risk of cervical intraepithelial neoplasia grades 2 and 3.the association between human papillomavirus 31 (hpv31) dna loads and the risk of cervical intraepithelial neoplasia grades 2 and 3 (cin2-3) was evaluated among women enrolled in the atypical squamous cells of undetermined significance (ascus) and low-grade squamous intraepithelial lesion (lsil) triage study (alts), who were monitored semiannually over 2 years and who had hpv31 infections detected at ≥1 visit. hpv31 dna loads in the first hpv31-positive samples and in a random set of the last po ...201526292291
productive replication of human papillomavirus 31 requires dna repair factor nbs1.activation of the atm (ataxia telangiectasia-mutated kinase)-dependent dna damage response (ddr) is necessary for productive replication of human papillomavirus 31 (hpv31). we previously found that dna repair and homologous recombination (hr) factors localize to sites of hpv replication, suggesting that atm activity is required to recruit factors to viral genomes that can productively replicate viral dna in a recombination-dependent manner. the mre11-rad50-nbs1 (mrn) complex is an essential comp ...201424850735
a dna methylation classifier of cervical precancer based on human papillomavirus and human genes.testing for high-risk (hr) types of human papillomavirus (hpv) is highly sensitive as a screening test of high-grade cervical intraepithelial neoplastic (cin2/3) disease, the precursor of cervical cancer. however, it has a relatively low specificity. our objective was to develop a prediction rule with a higher specificity, using combinations of human and hpv dna methylation. exfoliated cervical specimens from colposcopy-referral cohorts in london were analyzed for dna methylation levels by pyros ...201424535756
sequence variation of human papillomavirus type 31 long control region: phylogenetic and functional implications.about one-third of human papillomavirus (hpv) types infect the anogenital tract. high-risk genital hpv types (such as hpv 16, 18, 31, 33, and 35) are linked causally to the development of cervical cancer. the long control region (lcr) of the hpv genome regulates the replication and transcription of the viral genome. in this study, the functional significance of nucleotide sequence variation within the lcr of hpv 31 was investigated. the lcr was amplified by polymerase chain reaction (pcr) from 4 ...201323508911
coexistent squamous cell carcinoma and adenoid basal carcinoma in the uterine cervix and infection with human papillomavirus (hpv 31).adenoid basal carcinoma (abc) is an uncommon neoplasm of the uterine cervix. abc can be accompanied by carcinoma in situ or invasive carcinoma. most cases are discovered accidentally during radical hysterectomy. abc is associated with a high risk of human papillomavirus infection (hpv), most often hpv 16 infection.201324075382
novel e6 and e7 oncogenes variants of human papillomavirus type 31 in brazilian women with abnormal cervical cytology.hpv-31 has been widely described as an important oncogenic type, showing high incidence in worldwide and especially in northeastern brazil. we sought to identify the presence of specific mutations in hpv-31 e6 and e7 oncogenes in women with abnormal cervical smear. we enrolled 150 gynecological patients from sergipe state, northeastern brazil. hpv screening was carried out by polymerase chain reaction (my09/11). e6 and e7 oncogenes were amplified with specific primers and sequenced. the sequence ...201323403356
persistence of newly detected human papillomavirus type 31 infection, stratified by variant lineage.variants of human papillomavirus (hpv) type 31 have been shown to be related both to risk of cervical lesions and racial composition of a population. it is largely undetermined whether variants differ in their likelihood of persistence. study subjects were women who participated in the ascus-lsil triage study and who had a newly detected hpv31 infection during a two-year follow-up with six-month intervals. hpv31 isolates were characterized by sequencing and assigned to one of three variant linea ...201322729840
association of human papillomavirus type 31 variants with risk of cervical intraepithelial neoplasia grades 2-3.although the lineages of human papillomavirus type 31 (hpv31) variants are recognized, their clinical relevance is unknown. the purpose of our study was to examine risk of cervical intraepithelial neoplasia grades 2-3 (cin2/3) by hpv31 variants. study subjects were women who participated in the atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion triage study and who had hpv31 infections detected at one or more visits. they were followed semi-annuall ...201222396129
differentiation-dependent changes in levels of c/ebpβ repressors and activators regulate human papillomavirus type 31 late gene expression.the liver-enriched transcriptional activator protein (lap) isoform of ccaat/enhancer binding protein β (c/ebpβ) is shown to be a major activator of differentiation-dependent human papillomavirus (hpv) late gene expression, while the liver-enriched inhibitory protein (lip) isoform negatively regulates late expression. in undifferentiated cells, lips act as dominant-negative repressors of late expression, and upon differentiation, lip levels are significantly reduced, allowing lap-mediated activat ...201222379085
[establishment of the human papillomavirus type 31 positive cervical cancer cell line].the establishment of in vitro model will provide optimal conditions for the study of human papillomavirus (hpv)-associated cervical cancer. in this study, e6 and e7 gens of hpv31 were cloned and expressed in e. coli. the recombinant proteins were purified and used as antigens to immunize mice for the production of polyclonal antibody. mammalian expression plasmid pbudce4. 1-hpv31-e6/e7 was also constructed and transfected into c33a cells. the transfected cells were then selected by zeocin. the e ...201223233933
nuclear accumulation of the papillomavirus e1 helicase blocks s-phase progression and triggers an atm-dependent dna damage response.replication of the papillomavirus genome is initiated by the assembly of a complex between the viral e1 and e2 proteins at the origin. the e1 helicase is comprised of a c-terminal atpase/helicase domain, a central domain that binds to the origin, and an n-terminal regulatory region that contains nuclear import and export signals mediating its nucleocytoplasmic shuttling. we previously reported that nuclear accumulation of e1 has a deleterious effect on cellular proliferation which can be prevent ...201121734051
new variants of e6 and e7 oncogenes of human papillomavirus type 31 identified in northeastern brazil.objective: we sought to characterize e6 and e7 oncogenes genetic variability of hpv-31 isolated from cervical scraping samples of northeastern brazilian women. methods: e6 and e7 were amplified with specific primers, cloned and sequenced. the sequences obtained were aligned with the genbank reference sequences with the aim of evaluating the possible genetic variants. results: we identified several genetic variants in e6 and e7 sequences from hpv-31 positive women. three nucleotide changes in e6 ...201121802716
bowen's disease on the sole associated with human papillomavirus type 31. 201020629841
nuclear export of human papillomavirus type 31 e1 is regulated by cdk2 phosphorylation and required for viral genome maintenance.the initiator protein e1 from human papillomavirus (hpv) is a helicase essential for replication of the viral genome. e1 contains three functional domains: a c-terminal enzymatic domain that has atpase/helicase activity, a central dna-binding domain that recognizes specific sequences in the origin of replication, and a n-terminal region necessary for viral dna replication in vivo but dispensable in vitro. this n-terminal portion of e1 contains a conserved nuclear export signal (nes) whose functi ...201020844047
identification of neutralizing conformational epitopes on the human papillomavirus type 31 major capsid protein and functional implications.the aim of this study was to characterize the conformational neutralizing epitopes of the major capsid protein of human papillomavirus type 31. analysis of the epitopes was performed by competitive epitope mapping using 15 anti-hpv31 and by reactivity analysis using a hpv31 mutant with an insertion of a seven-amino acid motif within the fg loop of the capsid protein. fine mapping of neutralizing conformational epitopes on hpv l1 was analyzed by a new approach using a system displaying a combinat ...200919533761
detection of human papillomavirus type 31-neutralizing antibodies from naturally infected patients by an assay based on intracellular assembly of luciferase-expressing pseudovirions.the aim of this study was to develop a highly sensitive human papillomavirus type 31 (hpv31) neutralization assay based on the production of pseudovirions carrying luciferase. neutralizing antibodies against hpv31 were investigated in a set of hpv31 monoclonal antibodies and in women with evidence of hpv31 infection. neutralizing antibodies were detected in 78% of subjects with a positive enzyme-linked immunosorbent assay.200817989337
caveolin-1-dependent infectious entry of human papillomavirus type 31 in human keratinocytes proceeds to the endosomal pathway for ph-dependent uncoating.high-risk human papillomaviruses (hpvs) are small nonenveloped dna viruses with a strict tropism for squamous epithelium. the viruses are causative agents of cervical cancer and some head and neck cancers, but their differentiation-dependent life cycles have made them difficult to study in simple cell culture. thus, many aspects of early hpv infection remain mysterious. we recently showed the high-risk hpv type 31 (hpv31) enters its natural host cell type via caveola-dependent endocytosis, a dis ...200818667513
virus activated filopodia promote human papillomavirus type 31 uptake from the extracellular matrix.human papillomaviruses (hpvs), etiological agents of epithelial tumors and cancers, initiate infection of basal human keratinocytes (hks) facilitated by wounding. virions bind to hks and their secreted extracellular matrix (ecm), but molecular roles for wounding or ecm binding during infection are unclear. herein we demonstrate that hpv31 activates signals promoting cytoskeletal rearrangements and virion transport required for internalization and infection. activation of tyrosine and pi3 kinases ...200818834609
induction of antibody response against hepatitis e virus (hev) with recombinant human papillomavirus pseudoviruses expressing truncated hev capsid proteins in mice.a hepatitis e virus (hev) vaccine would be valuable to reduce the morbidity and mortality associated with the infection in endemic areas. hev pseudocapsids and epidermal delivery of hev orf2 dna vaccine by gene-gun have been shown to confer protection against virus challenge in monkeys. vectorization of a dna vaccine by virus-like particles is a new immunization approach. we report here the successful immunization of mice with two orf2 genes encapsidated into human papillomavirus type 31 virus-l ...200818835319
regulation of human papillomavirus type 31 gene expression during the differentiation-dependent life cycle through histone modifications and transcription factor binding.the life cycle of high-risk human papillomaviruses is linked to epithelial differentiation with virion production restricted to highly differentiated suprabasal cells. two major viral promoters direct high-risk hpv gene expression and their activities are dependent upon differentiation. the early promoter controls initiation of transcripts at sites upstream of the e6 open reading frame and is active in both undifferentiated as well as differentiated cells. the late viral promoter directs transcr ...200818237759
analysis of the roles of e6 binding to e6tp1 and nuclear localization in the human papillomavirus type 31 life cycle.the e6 oncoproteins of high-risk human papillomaviruses provide important functions not only for malignant transformation but also in the productive viral life cycle. e6 proteins have been shown to bind to a number of cellular factors, but only a limited number of analyses have investigated the effects of these interactions on the viral life cycle. in this study, we investigated the consequences of hpv 31 e6 binding to e6tp1, a putative rap1 gap protein. hpv 16 e6 has been shown to bind as well ...200716999984
human papillomavirus type 31 uses a caveolin 1- and dynamin 2-mediated entry pathway for infection of human keratinocytes.papillomaviruses are species-specific and epitheliotropic dna viruses that cause tumors in their natural hosts. certain infections with genital human papillomavirus (hpv) types are causally related to cervical cancer development. most papillomaviruses are thought to infect cells via a clathrin-dependent pathway, yet no studies have determined the entry route in permissive host epithelial cells. employing fluorescently labeled and native virions, we tested the effects of dominant-negative and bio ...200717626097
increased human papillomavirus type 31 dna load in a verrucous high-grade intraepithelial neoplasia of a human immunodeficiency virus-infected patient with extensive bowenoid papulosis. 200717300265
type-specific and cross-reactive antibodies induced by human papillomavirus 31 l1/l2 virus-like particles.the aim of this study was to determine whether antibodies induced by human papillomavirus (hpv) type 31 l1/l2 virus-like particles (vlps) could cross-react with vlps of the closely related hpv-16 and distantly related hpv-11, and to investigate the potential role of the l2 protein in l1/l2 vlps in inducing cross-neutralizing antibodies. antisera were prepared from rabbits immunized with intact or denatured hpv-31 l1/l2 vlps. cross-reaction and cross-neutralization were analysed by western blotti ...200717577054
identification of type-specific and cross-reactive neutralizing conformational epitopes on the major capsid protein of human papillomavirus type 31.the majority of the neutralizing epitopes of papillomaviruses (pv) are conformation-specific and have not been fully characterised. studies have, to date, been limited to a few hpv types only. we analysed the epitopes on the major capsid protein (l1) of human papillomavirus (hpv) type 31 using monoclonal antibodies (mabs) generated against hpv-31 virus-like particles (vlps). the type-specific mabs against hpv-31 were all found to be neutralizing and recognized conformation-dependent epitopes. tw ...200616508703
p2x(5) and p2x(7) receptors in human warts and cin-612 organotypic raft cultures of human papillomavirus infected keratinocytes.purinergic receptors, which bind adenosine 5'-triphosphate (atp), are expressed on human cutaneous keratinocytes and in squamous cell carcinomas. studies on normal human epidermis and primary keratinocyte cultures have suggested that p2x(5) receptors are likely to be involved in keratinocyte differentiation and p2x(7) receptors are likely to be part of the machinery of end stage terminal differentiation/apoptosis of keratinocytes. p2x(7) receptor agonists can significantly reduce primary keratin ...200618404488
regulation of human papillomavirus type 31 late promoter activation and genome amplification by protein kinase c.the life cycle of papillomaviruses is tightly linked to differentiation of host keratinocytes, but the mechanisms and cues by which life cycle events are tied to differentiation remain obscure. we have begun a systematic study of the differentiation-dependent life cycle of hpv31. a variety of signaling pathways have been implicated in controlling keratinocyte differentiation, especially the protein kinase c (pkc) pathway. we have used pharmacological inhibitors to determine that genome amplifica ...200616500689
genetic analysis of the human papillomavirus type 31 differentiation-dependent late promoter.human papillomaviruses infect stratifying squamous epithelia, causing benign and malignant lesions. upon differentiation of the host keratinocyte, the virus undergoes a dramatic increase in both dna replication and transcription from the late promoter, leading to expression of late genes and virion morphogenesis. in human papillomavirus type 31 (hpv31), the late promoter is designated p742 and includes multiple start sites embedded within the e7 gene. in this report, we mapped viral dna elements ...200515731225
induction of the human papillomavirus type 31 late promoter requires differentiation but not dna amplification.the human papillomavirus (hpv) life cycle is linked to the differentiation state of the host cell. in virus-infected undifferentiated basal epithelial cells, hpv genomes are maintained as episomes at low copy number. upon differentiation, a concomitant increase in viral copy number and an induction of late gene expression from a differentiation-specific promoter is seen. to investigate whether late gene expression was dependent on the amplification of the viral genome, inhibitors of dna replicat ...200515795277
the minor capsid protein l2 contributes to two steps in the human papillomavirus type 31 life cycle.prior studies, which have relied upon the use of pseudovirions generated in heterologous cell types, have led to sometimes conflicting conclusions regarding the role of the minor capsid protein of papillomaviruses, l2, in the viral life cycle. in this study we carry out analyses with true virus particles assembled in the natural host cell to assess l2's role in the viral infectious life cycle. for these studies we used the organotypic (raft) culture system to recapitulate the full viral life cyc ...200515767396
role of the e1--e4 protein in the differentiation-dependent life cycle of human papillomavirus type 31.the most highly expressed protein in the productive life cycle of human papillomaviruses (hpvs) is e1--e4, but its function is not well understood. to investigate the role of e1--e4, we undertook a genetic analysis in the context of the complete hpv type 31 (hpv31) genome. a mutant hpv31 genome (e4m9) was constructed that contained a stop codon in the e4 open reading frame at amino acid 9 and was silent in the overlapping e2 coding sequence. wild-type and mutant genomes were transfected into nor ...200515890911
human papillomavirus type 31 life cycle: methods for study using tissue culture models.the life cycle of human papillomaviruses (hpvs) has been difficult to study in tissue culture owing to its dependence on epithelial differentiation. in this chapter several methods are described to imitate the important steps in the hpv life cycle. normal human keratinocytes (nhks) harvested from neonatal foreskins were transfected with hpv type 31 genomes in order to generate stable cell lines containing episomal copies of hpv genomes. hpv-positive keratinocyte cultures were maintained in e med ...200515507718
polymorphism of human papillomavirus type 31 isolates infecting the genital tract of hiv-seropositive and hiv-seronegative women at risk for hiv infection.the genomic polymorphism of high-risk human papillomavirus (hpv) for types other than 16 has not been extensively described. we describe here the genomic polymorphism of high-risk hpv type 31 in 79 women (62 hiv-seropositive, 17 hiv-seronegative) by pcr-sequencing of the long control region (lcr), e6 and e7. lcr polymorphism was generated by 25 (6.4%) single-nucleotide variations over 391 bases. each variant compared to the prototype contained from 2 to 13 variations (mean of 9.4 +/- 3.3, median ...200515602735
human papillomavirus-31-related types predict better survival in cervical carcinoma.the aim of the current study was to explore the clinical implications and prognostic value of human papillomavirus (hpv) genotype in cervical carcinomas.200414716768
the binding of histone deacetylases and the integrity of zinc finger-like motifs of the e7 protein are essential for the life cycle of human papillomavirus type 31.the e7 oncoprotein of high-risk human papillomaviruses (hpvs) binds to and alters the action of cell cycle regulatory proteins such as members of the retinoblastoma (rb) family of proteins as well as the histone deacetylases (hdacs). to examine the significance of the binding of e7 to hdacs in the viral life cycle, a mutational analysis of the e7 open reading frame was performed in the context of the complete hpv type 31 (hpv-31) genome. human foreskin keratinocytes were transfected with wild-ty ...200415016876
role of the pdz domain-binding motif of the oncoprotein e6 in the pathogenesis of human papillomavirus type 31.a number of pdz domain-containing proteins have been identified as binding partners for the oncoprotein e6 of the high-risk type human papillomaviruses (hpvs). these include hdlg, hscrib, magi-1, magi-2, magi-3, and mupp1. the pdz domain-binding motif (-x-t-x-v) at the carboxy terminus of e6 is essential for targeting pdz proteins for proteasomal degradation. the presence of this motif only in the high-risk hpvs suggests its possible role in hpv-induced oncogenesis. to investigate the role of th ...200415507623
elevated amount of human papillomavirus 31 dna in a squamous cell carcinoma developed from bowenoid papulosis.a 50-year-old woman presented with asymptomatic, multiple black macules on the genitalia for 6 months. she presented multiple, round to irregularly shaped, black macules on her labia major and perineum. a keratotic reddish nodule was found on one of the macules. the results of laboratory investigations showed pancytopenia and a decreased cd4/cd8 ratio. a lymphocyte stimulation test showed a decreased response. the histological examination of a biopsy specimen led us to the diagnosis of bowenoid ...200415539898
genetic and biochemical analysis of cis regulatory elements within the keratinocyte enhancer region of the human papillomavirus type 31 upstream regulatory region during different stages of the viral life cycle.using linker scanning mutational analysis, we recently identified potential cis regulatory elements contained within the 5' upstream regulatory region (urr) domain and auxiliary enhancer (ae) region of the human papillomavirus type 31 (hpv31) urr involved in the regulation of e6/e7 promoter activity at different stages of the viral life cycle. for the present study, we extended the linker scanning mutational analysis to identify potential cis elements located in the keratinocyte enhancer (ke) re ...200414694093
infection, replication, and cytopathology of human papillomavirus type 31 in trophoblasts.human papillomavirus (hpv) dna is preferentially found in spontaneous abortions, specifically residing in trophoblasts, and transfected hpv-16 dna replicates and produces progeny in 3a trophoblasts in culture. in this study 3a trophoblasts were shown to display both hpv receptors and infection by hpv-31b and hpv-6 virus resulted in de novo (increasing) hpv dna replication in these cells (inhibited by neutralizing anti-hpv31b antibodies). reverse transcription-polymerase chain reaction analysis r ...200314644610
human papillomavirus type 31 e5 protein supports cell cycle progression and activates late viral functions upon epithelial differentiation.the function of the e5 protein of human papillomaviruses (hpv) is not well characterized, and controversies exist about its role in the viral life cycle. to determine the function of e5 within the life cycle of hpv type 31 (hpv31) we first constructed hpv31 mutant genomes that contained an altered aug initiation codon or stop codons in e5. cell lines were established which harbored transfected wild-type or e5 mutant hpv31 genomes. these cell lines all maintained episomal copies of hpv31 and reve ...200312584305
induction of the upstream regulatory region of human papillomavirus type 31 by dexamethasone is differentiation dependent.glucocorticoids have been shown to play a role in the transforming abilities of human papillomaviruses (hpvs), and glucocorticoid response elements (gres) have been identified in the upstream regulatory regions (urrs) of various hpv types. these findings have made glucocorticoids potential therapeutic targets for hpv infection. we have previously shown that the urr of hpv type 31 (hpv31) is insensitive to induction by the synthetic glucocorticoid dexamethasone (dex) in monolayer culture, despite ...200314512546
the upstream regulatory region of human papillomavirus type 31 is insensitive to glucocorticoid induction.the upstream regulatory region (urr) of various types of human papillomaviruses (hpvs) has been shown to contain functional glucocorticoid response elements (gres), including hpv type 11 (hpv11), hpv16, and hpv18. glucocorticoids have been demonstrated to induce the transcriptional activity of the early promoters of these hpv types. although it has been assumed that the urr of hpv31 contains at least one gre, no functionality has been demonstrated. we attempt to show here inducibility of the urr ...200212208949
long-term effect of interferon on keratinocytes that maintain human papillomavirus type 31.the long-term effects of interferon treatment on cell lines that maintain human papillomavirus type 31 (hpv-31) episomes have been examined. high doses and prolonged interferon treatment resulted in growth arrest of hpv-positive cells, with a high percentage of cells undergoing apoptosis. these effects were not seen with interferon treatment of either normal human keratinocytes or cells derived from hpv-negative squamous carcinomas, which exhibited only slight decreases in their rates of growth. ...200212163606
the human papillomavirus type 31 late 3' untranslated region contains a complex bipartite negative regulatory element.the papillomavirus life cycle is tightly linked to epithelial cell differentiation. production of virus capsid proteins is restricted to the most terminally differentiated keratinocytes in the upper layers of the epithelium. however, mrnas encoding the capsid proteins can be detected in less-differentiated cells, suggesting that late gene expression is controlled posttranscriptionally. short sequence elements (less than 80 nucleotides in length) that inhibit gene expression in undifferentiated e ...200212021332
genetic analysis of cis regulatory elements within the 5' region of the human papillomavirus type 31 upstream regulatory region during different stages of the viral life cycle.the function of the 5' region of the upstream regulatory region (urr) in regulating e6/e7 expression in cancer-associated papillomaviruses has been largely uncharacterized. in this study we used linker-scanning mutational analysis to identify potential cis regulatory elements contained within a portion of the 5' region of the urr that are involved in regulating transcription of the e6/e7 promoter at different stages of the viral life cycle. the mutational analysis illustrated differences in the ...200211967297
human papillomavirus type 31 replication modes during the early phases of the viral life cycle depend on transcriptional and posttranscriptional regulation of e1 and e2 expression.the e1 and e2 proteins are both required for papillomavirus dna replication, and replication efficiency is controlled by the abundance of these factors. in human papillomaviruses (hpvs), the regulation of e1 and e2 expression and its effect on viral replication are not well understood. in particular, it is not known if e1 and e2 modulate their own expression and how posttranscriptional mechanisms may affect the levels of the replication proteins. previous studies have implicated splicing within ...200211836404
interferon-inducible genes are major targets of human papillomavirus type 31: insights from microarray analysis. 200111790877
differentiation-dependent chromatin rearrangement coincides with activation of human papillomavirus type 31 late gene expression.the life cycle of human papillomaviruses (hpvs) is tightly linked to the differentiation status of the host cell. while early genes are expressed during the initial stages of viral infection, late gene expression occurs in the suprabasal layers of the cervical epithelium. late genes encode e1-e4, a cytosolic protein, and capsid proteins l1 and l2. we have mapped over 30 initiation sites for late transcripts and show that the transcripts initiate in a 200-nucleotide region within the e7 open read ...200111559836
early polyadenylation signals of human papillomavirus type 31 negatively regulate capsid gene expression.the l1 and l2 capsid genes of human papillomavirus type 31 (hpv-31) are expressed upon keratinocyte differentiation from a promoter located in the e7 open reading frame (orf) of the early region. late transcripts must therefore pass through and ignore the early polyadenylation sequences to use the downstream late aauaaa element located at the end of the l1 orf. to identify sequences which modulate downstream capsid gene expression, a variety of substitution mutations were introduced into the ear ...200111483760
the e8 domain confers a novel long-distance transcriptional repression activity on the e8e2c protein of high-risk human papillomavirus type 31.infections with high-risk human papillomaviruses (hpvs) are the major risk factor for the development of anogenital cancers. viral e2 proteins are involved in viral dna replication and regulation of transcription. repression of the viral p97 promoter by e2 proteins has been implicated in the modulation of the immortalization capacity and dna replication properties of high-risk hpvs. analysis of the cis and trans requirements for repression of the hpv type 31 (hpv31) p97 promoter, however, reveal ...200111287563
chemical shift mapped dna-binding sites and 15n relaxation analysis of the c-terminal kh domain of heterogeneous nuclear ribonucleoprotein k.the k homology (kh) motif is one of the major classes of nucleic acid binding proteins. some members of this family have been shown to interact with dna while others have rna targets. there have been no reports containing direct experimental evidence regarding the nature of kh module-dna interaction. in this study, the interaction of the c-terminal kh domain of heterogeneous nuclear ribonucleoprotein k (kh3) with its cognate single-stranded dna (ssdna) are investigated. chemical shift perturbati ...200010821674
microarray analysis identifies interferon-inducible genes and stat-1 as major transcriptional targets of human papillomavirus type 31.human papillomaviruses (hpvs) infect keratinocytes and induce proliferative lesions. in infected cells, viral gene products alter the activities of cellular proteins, such as rb and p53, resulting in altered cell cycle response. it is likely that hpv gene products also alter expression of cellular genes. in this study we used microarray analysis to examine the global changes in gene expression induced by high-risk hpv type 31 (hpv31). among 7,075 known genes and ests (expressed sequence tags) te ...200010756030
the e8e2c protein, a negative regulator of viral transcription and replication, is required for extrachromosomal maintenance of human papillomavirus type 31 in keratinocytes.the viral e2 protein is a major regulator of papillomavirus dna replication. an important way to influence viral replication is through modulation of the activity of the e2 protein. this could occur through the action of truncated e2 proteins, called e2 repressors, whose role in the replication cycle of human papillomaviruses (hpvs) has not been determined. in this study, using cell lines that contain episomal copies of the "high-risk" hpv type 31 (hpv31), we have identified viral transcripts wi ...200010627528
regulation of human papillomavirus type 31 polyadenylation during the differentiation-dependent life cycle.the l1 and l2 capsid genes of human papillomavirus type 31 (hpv-31) are expressed late in the differentiation-dependent life cycle from a promoter located in the e7 open reading frame (orf) of the early region. these late hpv genes are transcribed by rna polymerase ii which reads through the region containing early polyadenylation signals and proceeds to a poly(a) site downstream of l1. in this study, we have investigated the mechanisms regulating differentiation-dependent polyadenylation and re ...199910438805
human papillomavirus type 31 oncoproteins e6 and e7 are required for the maintenance of episomes during the viral life cycle in normal human keratinocytes.the e6 and e7 oncoproteins of the high-risk human papillomavirus (hpv) types are able to immortalize human keratinocytes in vitro and likely contribute to the development of anogenital malignancies in vivo. the role of these oncoproteins in the productive viral life cycle, however, is not known. to begin to examine these possible roles, mutations in e6 were introduced in the context of the complete hpv 31 genome. although transfected wild-type hpv 31 genomes, as well as genomes containing an e6 ...199910411895
differentiation-induced changes in promoter usage for transcripts encoding the human papillomavirus type 31 replication protein e1.the life cycle of human papillomaviruses (hpvs) is tied to keratinocyte differentiation. one key event in the viral life cycle is the differentiation-dependent increase in viral replication. this increase in replication activity results in an amplification of the hpv genome from approximately 50 copies per cell in basal keratinocytes to thousands of copies of the viral genome per cell in suprabasal keratinocytes. to characterize the events associated with this differentiation-dependent increase ...199910208937
dna replication of human papillomavirus type 31 is modulated by elements of the upstream regulatory region that lie 5' of the minimal origin.the viral replication factors e1 and e2 of papillomaviruses are necessary and sufficient to replicate plasmids containing the minimal origin of dna replication in transient assays. under physiological conditions, the upstream regulatory region (urr) governs expression of the early viral genes. to determine the effect of urr elements on e1 and e2 expression specifically, and on the regulation of dna replication during the various phases of the viral life cycle, we carried out a systematic replica ...19999971761
transactivation by the e2 protein of oncogenic human papillomavirus type 31 is not essential for early and late viral functions.the activation of transcription and of dna replication are, in some cases, mediated by the same proteins. a prime example is the e2 protein of human papillomaviruses (hpvs), which binds accn6ggt sequences and activates heterologous promoters from multimerized binding sites. the e2 protein also has functions in replication, where it complexes with the virally encoded origin recognition protein, e1. much of the information on these activities is based on transient-transfection assays as well as bi ...19989733852
differential requirements for conserved e2 binding sites in the life cycle of oncogenic human papillomavirus type 31.human papillomavirus (hpv) e2 proteins regulate viral replication by binding to sites in the upstream regulatory region (urr) and by complex formation with the e1 origin recognition protein. in the genital hpv types, the distribution and location of four e2 binding sites (bs1 to bs4) which flank a single e1 binding site are highly conserved. we have examined the roles of these four e2 sites in the viral life cycle of hpv type 31 (hpv31) by using recently developed methods for the biosynthesis of ...19989445001
differential effects of the splice acceptor at nucleotide 3295 of human papillomavirus type 31 on stable and transient viral replication.in human papillomavirus type 31 (hpv-31), the e1--e4 and e5 open reading frames are expressed from polycistronic mrnas. the major polycistronic mrnas which encode e1--e4 and e5 are spliced messages which utilize a splice acceptor at nucleotide (nt) 3295 (spa3295). our laboratory recently developed a recombinant system for the synthesis of hpvs following immortalization of primary keratinocytes with cloned hpv-31 genomes (m. g. frattini et al., proc. natl. acad. sci. usa 93:3062-3067, 1996). thes ...19979343169
squamous cell carcinoma of the endometrium with human papillomavirus type 31. 19979154764
squamous cell carcinoma of the endometrium with human papillomavirus type 31 and without tumor suppressor gene p53 mutation.primary squamous cell carcinoma of the endometrium (escc) is extremely rare. there has been no report of human papillomavirus (hpv) detected in escc. a 64-year-old japanese female underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, and dissection of the pelvic, para-aortic, and bilateral inguinal lymph nodes. the tumor was confined to the endometrium, without invasion of myometrium or cervix. the endometrium was seen to be replaced by moderately differentiated squamous cell ...19979103411
the 5' region of the human papillomavirus type 31 upstream regulatory region acts as an enhancer which augments viral early expression through the action of yy1.cis-elements which control human papillomavirus early gene expression have previously been localized to sequences in the upstream regulatory region (urr) which are proximal to the e6 open reading frame. these elements include an enhancer element which functions preferentially in keratinocytes as well as promoter elements. the function of the remaining approximate 500-bp region of the urr in regulating viral expression in the high risk papillomaviruses has been largely uncharacterized. in hpv 6, ...19979344918
solution structure of the dna-binding domain of a human papillomavirus e2 protein: evidence for flexible dna-binding regions.the three-dimensional structure of the dna-binding domain of the e2 protein from human papillomavirus-31 was determined by using multidimensional heteronuclear nuclear magnetic resonance (nmr) spectroscopy. a total of 1429 nmr-derived distance and dihedral angle restraints were obtained for each of the 83-residue subunits of this symmetric dimer. the average root mean square deviations of 20 structures calculated using a distance geometry-simulated annealing protocol are 0.59 and 0.90 angstroms ...19968652551
human papillomavirus type 31 dna detected in part of the dysplasia but in no part of the squamous metaplasia in a specimen taken from one patient.using in situ hybridization, human papillomavirus (hpv 6, 16, 18, 31, 33) dnas were detected in a cervical severe dysplasia accompanied by squamous metaplasia. it was found that, only hpv 31 dna was harbored in the cervical severe dysplasia, but hpv dnas were not identified in a lesion of squamous metaplasia. the in situ hybridization method will be of use, therefore, when dysplasia with squamous metaplasia or other lesions are examined for hpv dna. in a cervical smear, hpv 31 dna could be detec ...19911648636
cervical human papillomavirus deoxyribonucleic acid and cytologic evaluations in gynecologic outpatients.we studied the prevalence and cytologic manifestations of human papillomavirus deoxyribonucleic acid among 2668 gynecologic outpatients. the study population consisted of 1573 women who came into the emergency room, 623 women from an abortion clinic who were seen because of induced first-trimester abortion, and 472 women who had been referred to a colposcopy clinic because of an abnormal papanicolaou smear finding. a dot blot technique was used for the detection of human papillomavirus types 6/1 ...19911852101
human papillomavirus type 31 infection of the uterine cervix in england.a total of 452 uterine cervical scrapes, from two centres in england, has been examined by dot blot hybridisation for the presence of human papilloma virus (hpv) types 6, 11, 16, 18 and 31. hpv dna was found in 36.5% samples. twenty-nine of the women were infected with more than one type. of those with detectable hpv, 14.5% had hpv type 31 infections. this type appears to cause significant infection of the genital tract in england.19892545788
nucleotide sequence of human papillomavirus type 31: a cervical neoplasia-associated virus.the nucleotide sequence of human papillomavirus (hpv) 31 dna (7912 bp) was determined and used to deduce the genomic organization of this cervical cancer-associated virus. based on comparisons of the hpv 31 dna sequence to other sequenced hpvs, hpv 31 is a typical papillomavirus most related to hpv 16 (70% identical nucleotides). the e6 and e7 open reading frames (orf) of hpv 31 contain several potential dna binding motifs (cys-x-x-cys), the locations of which are conserved in all hpvs. the e6 o ...19892545036
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