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the human papilloma virus (hpv)-18 e6 oncoprotein physically associates with tyk2 and impairs jak-stat activation by interferon-alpha.we have examined the effects of human papilloma virus (hpv) e6 proteins on interferon (ifn) signaling. here we show that expression of the 'malignant' hpv-18 e6 in human ht1080 cells results in inhibition of jak-stat activation in response to ifn-alpha but not ifn-gamma. this inhibitory effect is not shared by the 'benign' hpv-11 e6. the dna-binding and transactivation capacities of the transcription factor isgf3 are diminished in cells expressing hpv-18 e6 after ifn-alpha treatment as a result ...199910523853
purification of virus-like particles of recombinant human papillomavirus type 11 major capsid protein l1 from saccharomyces cerevisiae.recombinant major capsid protein, l1 (m(r) = 55,000), of human papillomavirus type 11 was expressed intracellularly at high levels in a galactose-inducible saccharomyces cerevisiae expression system by an hpv6/11 hybrid gene. the capsid protein self-assembled into virus-like particles (vlps) and accounted for 15% of the total soluble protein. a purification process was developed that consisted of two main steps: microfiltration and cation-exchange chromatography. the purified vlps were 98% homog ...199910600468
replication-associated activities of purified human papillomavirus type 11 e1 helicase.replication of human papillomavirus type11 (hpv11) requires both the e1 and the e2 proteins. e1 is structurally and functionally similar to sv40 large t-antigen and is a dna helicase/ntpase that binds to the origin of replication and initiates viral dna replication. the biochemical characterization of hpv e1 is incompletely documented in the literature in part because of difficulties in expressing and purifying the protein. herein, we report a method for the overexpression of full-length, untagg ...200010686145
subunit affinities and stoichiometries of the human papillomavirus type 11 e1:e2:dna complex.the association between the papillomavirus e1 and e2 proteins is an important regulatory interaction, imparting coordinated control of viral transcription and replication. using fluorescence polarization, we have characterized the interactions between hpv-11 e1, hpv-11 e2, and dna in solution at equilibrium. for these studies, two double-stranded fluorescein-labeled oligonucleotides were prepared. the first fluorescent oligonucleotide, designated fl-e2bs and containing a single e2 binding-site p ...199910194380
the human papillomavirus type 11 e1e4 protein is phosphorylated in genital epithelium.the most abundant viral transcript in human papillomavirus (hpv) 11-infected xenograft tissue has been shown to encode the e1(wedge)e4 protein. the function of e1(wedge)e4 protein has not been determined. several potential phosphorylation sequence motifs were identified in the hpv 11 e1(wedge)e4 protein, including potential sites of phosphorylation by mitogen-activated protein kinase (mapk), camp-dependent protein kinase (pka), casein kinase ii, and protein kinase c. to test phosphorylation of t ...200010704351
transmission of human papillomavirus type 11 infection by desquamated cornified cells.while much is known about the human papillomavirus (hpv) productive cycle, the mechanisms of virion transmission from person to person are poorly understood. the keratinocyte is the target cell of hpv infection. as keratinocytes differentiate, nuclei are lost and the cornified cell envelope develops. layers of these desquamated cornified cells (dccs) are continuously shed from the stratum corneum. release of hpv requires the cornified cell envelope, a normally very durable structure, to break ap ...200111222093
human papillomavirus type 11 recombinant l1 capsomeres induce virus-neutralizing antibodies.the human papillomavirus type 11 (hpv-11) l1 major capsid protein can be trypsinized to generate recombinant capsomeres that retain hpv genotype-restricted capsid antigenicity (m. li, t. p. cripe, p. a. estes, m. k. lyon, r. c. rose, and r. l. garcea, j. virol. 71:2988-2995, 1997). in the present study, hpv-11 virion-neutralizing monoclonal antibodies h11.f1 and h11.h3, previously characterized as recognizing two distinct hpv-11 capsid-neutralizing antigenic domains (s. w. ludmerer, d. benincasa ...19989621080
the hinge of the human papillomavirus type 11 e2 protein contains major determinants for nuclear localization and nuclear matrix association.the e2 protein of papillomaviruses is a site-specific dna binding nuclear protein. it functions as the primary replication origin recognition protein and assists in the assembly of the preinitiation complex. it also helps regulate transcription from the native viral promoter. the e2 protein consists of an amino-terminal (n) trans-acting domain, a central hinge (h) domain, and a carboxyl-terminal (c) protein dimerization and dna binding domain. the hinge is highly divergent among papillomaviruses ...200010729151
the e1 helicase of human papillomavirus type 11 binds to the origin of replication with low sequence specificity.expression of the human papillomavirus type 11 e1 and e2 genes is necessary and sufficient to support viral dna replication. the full-length e2 protein is a transcriptional modulator that also interacts with the e1 helicase to form an e1/e2 complex at the viral origin of replication. previous studies indicated that efficient binding of this complex to the replication origin is site-specific and that the e2 homodimer was required for efficient e1 binding. human papillomavirus type 11 e2 and e1 pr ...200010792994
concurrent respiratory and cutaneous papillomatosis with human papillomavirus type 11. 200212447245
abnormalities of cornified cell envelopes isolated from human papillomavirus type 11-infected genital epithelium.keratinocytes are the predominant cells in human skin. as keratinocytes differentiate, the nuclei are lost and the cornified cell envelope (cce) develops, forming a covalently cross-linked, insoluble structure under the cell membrane. layers of anuclear cces in the stratum corneum provide a barrier against water loss and mechanical damage and are a first line of immunologic defense. infection of keratinocytes with human papillomaviruses (hpvs) induces proliferation and abnormalities including re ...200010814571
identification of domains of the human papillomavirus type 11 e1 helicase involved in oligomerization and binding to the viral origin.the e1 helicase of papillomavirus is required, in addition to host cell dna replication factors, during the initiation and elongation phases of viral episome replication. during initiation, the viral e2 protein promotes the assembly of enzymatically active multimeric e1 complexes at the viral origin of dna replication. in this study we used the two-hybrid system and chemical cross-linking to demonstrate that human papillomavirus type 11 (hpv11) e1 can self-associate in yeast and form hexamers in ...200010906188
association of the human papillomavirus type 11 e1()e4 protein with cornified cell envelopes derived from infected genital epithelium.the cornified cell envelope (cce) is an insoluble matrix of covalently linked proteins assembled in differentiating keratinocytes, providing a barrier against external insults. cces derived from hpv 11-infected tissue are fragile compared to those derived from healthy epithelium. to study a possible role for the e1()e4 protein, hpv 11-infected epithelium was examined for the distribution of this protein and three cce proteins. cces were then purified from genital epithelium, fragmented, washed t ...200011080474
neutralization of human papillomavirus (hpv) pseudovirions: a novel and efficient approach to detect and characterize hpv neutralizing antibodies.the development of vaccines against human papillomaviruses (hpvs) has long been hampered by the inability to grow hpvs in tissue culture and the lack of an efficient neutralization assay. to date, less than 10% of more than 100 different hpv types can be grown in athymic and "scid" mouse xenograft systems or raft culture systems. recently, the in vitro generation of hpv pseudovirions and their use in neutralization assays were demonstrated. the major shortcomings of the current approaches to hpv ...200011118379
human papillomavirus virus-like particles are efficient oral immunogens when coadministered with escherichia coli heat-labile enterotoxin mutant r192g or cpg dna.certain human papillomaviruses (hpvs) cause most cervical cancer, which remains a significant source of morbidity and mortality among women worldwide. hpv recombinant virus-like particles (vlps) are promising vaccine candidates for controlling anogenital hpv disease and are now being evaluated as a parenteral vaccine modality in human subjects. vaccines formulated for injection generally are more costly, more difficult to administer, and less acceptable to recipients than are mucosally administe ...200111312347
infection with the oncogenic human papillomavirus type 59 alters protein components of the cornified cell envelope.infection of the genital tract with human papillomaviruses (hpvs) leads to proliferative and dysplastic epithelial lesions. the mechanisms used by the virus to escape the infected keratinocyte are not well understood. infection of keratinocytes with hpv does not cause lysis, the mechanism used by many viruses to release newly formed virions. for hpv 11, a type associated with a low risk of neoplastic disease, the cornified cell envelope (cce) of infected keratinocytes is thin and fragile, and tr ...200312726726
interaction of human papillomavirus type 11 e7 protein with tap-1 results in the reduction of atp-dependent peptide transport.human papillomaviruses (hpvs) cause benign and malignant epithelial tumors of the respiratory and genital mucosa. we previously reported that recurrent respiratory papillomas caused by hpv 6/11 express low levels of antibody-detectable tap-1, the protein that transports peptides into the endoplasmic reticulum for assembly and presentation by mhc class i, and that the extent of tap-1 immunostaining is inversely related to the frequency of disease recurrence. we have now determined a mechanism for ...200111580231
a novel human papillomavirus type 6 neutralizing domain comprising two discrete regions of the major capsid protein l1.we have mapped the binding sites on human papillomavirus (hpv) type 6 for three hpv 6-specific neutralizing monoclonal antibodies (mabs). the critical binding residues were first identified by making hpv 11-like amino acid substitutions in the hpv 6 major capsid protein l1 and assaying the resulting virus-like particles (vlps) for reactivity with the mabs. to confirm the relevance of these residues for mab binding, we demonstrated that hpv 6 type-specificity could be transferred to hpv 11 vlps b ...200111689049
quantitative rt-pcr assay for hpv infection in cultured cells.early events in the life cycle of the human papillomaviruses (hpv) have been difficult to investigate due to both the scarcity of authentic hpv virions and limitations in assays to detect and quantify nonpermissive infections in monolayer cell culture. we have developed a quantitative reverse transcription-pcr (qrt-pcr) assay for the e1( wedge )e4 transcript of hpv-11. this assay is both sensitive, and capable of differentiating between infections caused by a wide range of virus input. the qrt-p ...200312880929
papillomavirus microbicidal activities of high-molecular-weight cellulose sulfate, dextran sulfate, and polystyrene sulfonate.the high-molecular-weight sulfated or sulfonated polysaccharides or polymers cellulose sulfate, dextran sulfate, and polystyrene sulfonate were tested for microbicidal activity against bovine papillomavirus type 1 (bpv-1) and human papillomavirus type 11 (hpv-11) and type 40 (hpv-40). in vitro assays included the bpv-1-induced focus-forming assay and transient infection of human a431 cells with hpvs. the compounds were tested for microbicidal activity directly by preincubation with virus prior t ...200111709319
a phase 1 study of a recombinant viruslike particle vaccine against human papillomavirus type 11 in healthy adult volunteers.viruslike particles (vlps) produced from the l1 protein of several papillomaviruses have induced protection from infection after live challenge in animal models. in the present study, the safety and immunogenicity of a human papillomavirus (hpv)--11 l1 vlp candidate vaccine were measured in a phase 1, dose-finding trial in humans. the vaccine was well tolerated and induced high levels of both binding and neutralizing antibodies. marked increases in lymphoproliferation to hpv--11 l1 antigens were ...200111319684
papillary immature metaplasia of the uterine cervix: a report of 5 cases with an emphasis on the differential diagnosis from reactive squamous metaplasia, high-grade squamous intraepithelial lesion and papillary squamous cell carcinoma.papillary immature metaplasia (pim) is a distinctive exophytic lesion of the uterine cervix and shares some histologic and cytologic features with ordinary squamous metaplasia (sm), atypical immature squamous metaplasia (aim), high-grade squamous intraepithelial neoplasia (hsil) and papillary squamous cell carcinoma (psc). pim has been suggested to be a subset of condyloma associated with low-risk type human papilloma virus (hpv), however, the etiologic role of hpv and biologic behavior of the d ...200111748359
expression of cytokeratin 16 in human papillomavirus type 11-infected genital epithelium.during normal keratinocyte differentiation, a coordinated expression of many cytoskeletal and regulatory proteins occurs. several studies suggest that expression of some of these proteins is altered in epithelium infected by the human papillomavirus (hpv). to examine protein expression, human foreskin tissue was infected with either the low-risk hpv type 11 or with hpv 83, a high-risk type. the foreskin tissue was implanted and grown in the athymic mouse xenograft system. immunohistochemistry an ...200211748664
induction of chemosensitivity in nasopharyngeal carcinoma cells using a human papillomavirus regulatory sequence and the thymidine kinase gene.nasopharyngeal carcinoma (npc) is a human cancer of epithelial cell origin. infection by epstein-barr virus has been shown to be closely associated with this tumor. recent studies have indicated that another common epitheliotropic virus, human papillomavirus (hpv), is also found in a significant number of npc cases. in this study, we evaluated the feasibility of using the hpv regulatory long control region (lcr) to drive the expression of the thymidine kinase (tk) gene to achieve chemosensitivit ...200211810024
adenoassociated virus type 2-induced inhibition of the human papillomavirus type 18 promoter in transgenic mice.the epithelium of the cervix uteri has been reported to be frequently coinfected with both human papillomaviruses (hpv) and helper virus-dependent adenoassociated viruses (aav). seroepidemiological data suggest that aav infection could inhibit cervical cancer that is caused by specific ("high-risk") types of papillomaviruses. in vitro, infection with aav type 2 (aav-2) or transfection of aav-2 early (rep) genes has been shown to inhibit transformation by papillomaviruses. to analyze the effects ...200211853410
poor antibody response against human papillomavirus in adult-onset laryngeal papillomatosis.to investigate whether adult-onset laryngeal papillomatosis induces serum antibodies to the human papillomavirus (hpv), 60 patients underwent a clinical examination, and hpv dna from their laryngeal biopsy was assayed by pcr and hpv serology with virus-like particles as the antigen. patients and controls (n = 53) showed no differences in their hpv 6 and 16 antibodies. patients more often had hpv 11 antibodies, female patients more often than female controls or male patients. of the female patien ...200111339256
antibody, cytokine and cytotoxic t lymphocyte responses in chimpanzees immunized with human papillomavirus virus-like particles.we evaluated antibody, cytokine (ifn-gamma, il-5, tnf-alpha), and cytotoxic t lymphocyte (ctl) responses in chimpanzees immunized with monovalent or quadrivalent (hpv-6, -11, -16, -18) l1 virus-like particle (vlp) vaccines administered i.m. on aluminum hydroxyphosphate (alum) at weeks 0, 8 and 24. maximum serum antibody titers to type-specific, neutralizing, conformational epitopes on hpv-11 or -16 l1 vlps were detected by radioimmunoassay (ria) four weeks after the second and third immunization ...200111395208
hybrid papillomavirus l1 molecules assemble into virus-like particles that reconstitute conformational epitopes and induce neutralizing antibodies to distinct hpv types.human papillomavirus (hpv) hybrid virus-like particles (vlps) were prepared using complementary regions of the major capsid l1 proteins of hpv-11 and -16. these hybrid l1 proteins were tested for assembly into vlps, for presentation and mapping of conformational neutralizing epitopes, and as immunogens in rabbits and mice. two small noncontiguous hypervariable regions of hpv-16 l1, when replaced into the hpv-11 l1 backbone, produced an assembly-positive hybrid l1 which was recognized by the type ...200111878901
human tata binding protein inhibits human papillomavirus type 11 dna replication by antagonizing e1-e2 protein complex formation on the viral origin of replication.the human papillomavirus (hpv) protein e2 possesses dual roles in the viral life cycle. by interacting directly with host transcription factors in basal keratinocytes, e2 promotes viral transcription. as keratinocyte differentiation progresses, e2 associates with the viral helicase, e1, to activate vegetative viral dna replication. how e2's major role switches from transcription to replication during keratinocyte differentiation is not understood, but the presence of a tata site near the viral o ...200211967317
early assessment of the efficacy of a human papillomavirus type 16 l1 virus-like particle vaccine.a post hoc analysis was performed using combined data from two phase i tolerability/immunogenicity studies of monovalent human papillomavirus type 11 (hpv11) or hpv16 l1 virus-like particle (vlp) vaccines. the goal was to determine if the hpv16 l1 vlp vaccine protected against hpv16 infection. vaccine or placebo was given at 0, 2 and 6 months. hpv16 infection was defined by positive polymerase chain reaction (pcr) results following vaccination. the incidence of hpv infection was observed to be 0 ...200415246630
cellular changes induced by low-risk human papillomavirus type 11 in keratinocytes that stably maintain viral episomes.infections by low-risk papillomavirus types, such as human papillomavirus (hpv) type 6 (hpv-6) and hpv-11, induce benign genital warts that rarely progress to malignancy. in contrast, lesions induced by high-risk hpv types have the potential to progress to cancer. considerable information is available concerning the pathogenesis of high-risk hpv types, but little is known about the life cycle of low-risk hpv types. although functionally distinct, both high- and low-risk virus types infect kerati ...200111462028
antibodies to human papillomavirus 16 l1 virus-like particles as an independent prognostic marker in cervical cancer.infection with high-risk human papillomavirus (hpv) types such as hpv-16 is a major risk factor for the development of cervical cancer. hpv-16 capsid antibodies are detectable in approximately 50% of patients with hpv-16 dna-positive cervical cancer. we investigated the prognostic significance of hpv capsid antibodies for survival in patients with cervical cancer in comparison with conventional clinicopathologic features such as staging, histologic grading, histology, age, and treatment modality ...200211967495
analysis of cd4(+) t-cell responses to human papillomavirus (hpv) type 11 l1 in healthy adults reveals a high degree of responsiveness and cross-reactivity with other hpv types.human papillomavirus type 11 (hpv-11) infection causes genital warts and recurrent respiratory papillomatosis. while there is compelling evidence that cd4(+) t cells play an important role in immune surveillance of hpv-associated diseases, little is known about human cd4(+) t-cell recognition of hpv-11. we have investigated the cd4(+) t-cell responses of 25 unrelated healthy donors to hpv-11 l1 virus-like particles (vlp). cd4(+) t-cell lines from 21 of 25 donors were established. cell sorting ex ...200212097554
priming of human papillomavirus type 11-specific humoral and cellular immune responses in college-aged women with a virus-like particle vaccine.in this study, we evaluated the potency of a human papillomavirus (hpv) virus-like particle (vlp)-based vaccine at generating hpv type 11 (hpv-11)-specific cellular and humoral immune responses in seronegative women. the vaccine was administered by intramuscular immunizations at months 0, 2, and 6. a fourth immunization was administered to approximately half of the women at month 12. all vaccine recipients had positive hpv-11 vlp-specific lymphoproliferative responses at month 3 following the se ...200212097595
human papillomavirus type 11 alters the transcription and expression of loricrin, the major cell envelope protein.human papillomavirus (hpv) does not induce lysis of infected keratinocytes, and the exact mechanisms of viral escape are not known. as keratinocytes differentiate, the cornified cell envelope (cce) develops, providing a protective barrier to the host. we previously showed that the normally durable cce in hpv 11-infected epithelium is fragile compared to cces in healthy epithelium. in this study, we examined uninfected and hpv 11-infected human genital epithelium for expression of loricrin, the m ...200212127787
[immunogenicity study of hpv 6b virus-like particles].to confirm human papillomavirus (hpv) 6b virus-like particles (vlp) have strong immunogenicity and the protective antibody induced by hpv 6b vlp have cross-reactive immunity against hpv11 vlp and bovine papillomavirus (bpv) 1 vlp.200212133476
molecular events in the progression of recurrent respiratory papillomatosis to carcinoma.identification of the type of human papillomavirus (hpv) by polymerase chain reaction and sequencing to determine coinfection or superinfection (by more than 1 hpv type) and other molecular events have not been reported in a series of patients exhibiting the morphologic spectrum of recurrent respiratory papillomatosis progressing to carcinoma.200212296755
the l1 major capsid protein of human papillomavirus type 11 interacts with kap beta2 and kap beta3 nuclear import receptors.we have previously shown that the l1 major capsid protein of low-risk hpv11 binds to the kap alpha2 adapter and enters the nucleus via a kap alpha2beta1-mediated pathway. in this study, we discovered that hpv11 l1 capsomeres bind to kap beta2 import receptor, known to mediate nuclear import of hnrnp a1 via interaction with its nuclear localization signal termed m9. significantly, binding of hpv11 l1 capsomeres to kap beta2 inhibited the nuclear import of kap beta2, and its specific m9-containing ...200312620808
human papillomavirus-specific antibody status in oral fluids modestly reflects serum status in human immunodeficiency virus-positive individuals.serological assays are valuable tools for studies of the epidemiology of human papillomaviruses (hpvs). the efficacy of a less invasive oral-fluid assay for detection of hpv antibodies was examined. matched serum, saliva, and oral mucosal transudate (omt) specimens collected from 150 human immunodeficiency virus-seropositive patients were tested for immunoglobulin g antibodies against hpv-6 and hpv-11 combined (hpv-6/11) and hpv-16 capsids. antibodies to hpv were detected in both types of oral s ...200312738644
discovery of the first series of inhibitors of human papillomavirus type 11: inhibition of the assembly of the e1-e2-origin dna complex.we have discovered a series of inhibitors of the assembly of the hpv11 e1-e2-origin dna complex, which incorporate an indandione fused to a substituted tetrahydrofuran.200312852961
mrna splicing regulates human papillomavirus type 11 e1 protein production and dna replication.the papillomavirus replicative helicase e1 and the origin recognition protein e2 are required for efficient viral dna replication. we fused the green fluorescent protein (gfp) to the human papillomavirus type 11 e1 protein either in a plasmid with the e1 coding region alone (nucleotides [nt] 832 to 2781) (pgfp-11e1) or in a plasmid containing both the e1 and e2 regions (nt 2723 to 3826) and the viral origin of replication (ori) (p11rc). the former supported transient replication of an ori plasmi ...200312970406
suppression of human papillomavirus gene expression in vitro and in vivo by herpes simplex virus type 2 infection.recent epidemiological studies have found that women infected with both herpes simplex virus type 2 (hsv-2) and human papillomavirus (hpv) type 16 or hpv-18 are at greater risk of developing cervical carcinoma compared to women infected with only one virus. however, it remains unclear if hsv-2 is a cofactor for cervical cancer or if hpv and hsv-2 interact in any way. we have studied the effect of hsv-2 infection on hpv-11 gene expression in an in vitro double-infection assay. hpv transcripts wer ...200314517068
induction of productive human papillomavirus type 11 life cycle in epithelial cells grown in organotypic raft cultures.the study of the human papillomavirus (hpv) life cycle was hampered for more than 50 years by the lack of a conventional cell culture system for propagating hpv. considerable progress has been made in the production of several hpv types using either organotypic rafts or human epithelial xenografts in immunocompromised mice. in this study, we demonstrated episomal maintenance of hpv-11 dna in n-tert cells. hpv-11 episomal dna containing cell populations grown in raft culture showed induction of t ...200616460777
the histologic differentiation of oral condyloma acuminatum from its mimics.the purpose of this study was to determine which histologic features could enable one to distinguish oral condyloma, as defined by the detection of human papillomavirus (hpv) dna through in situ hybridization, from its mimics.200314561966
crystal structure of the e2 transactivation domain of human papillomavirus type 11 bound to a protein interaction inhibitor.interaction between the e2 protein and e1 helicase of human papillomaviruses (hpvs) is essential for the initiation of viral dna replication. we recently described a series of small molecules that bind to the n-terminal transactivation domain (tad) of hpv type 11 e2 and inhibits its interaction with e1 in vitro and in cellular assays. here we report the crystal structures of both the hpv11 tad and of a complex between this domain and an inhibitor, at 2.5- and 2.4-a resolution, respectively. the ...200414634007
[study on the frequency of human papillomavirus type 6 and type 11 infection and l1 gene expression of the virus in biopsy samples of pointed condyloma patients].to determine the different rates of human papillomavirus types 6 (hpv-6) and 11 (hpv-11) infection in biopsy samples from pointed condyloma patients, and to construct prokaryotic expression system of the major capsid protein l1 of the virus so as to establish an elisa for detecting the expression of l1 gene in the biopsy samples.200616749998
the human papillomavirus type 11 and 16 e6 proteins modulate the cell-cycle regulator and transcription cofactor trip-br1.the genital human papillomaviruses (hpvs) are a taxonomic group including hpv types that preferentially cause genital and laryngeal warts ("low-risk types"), such as hpv-6 and hpv-11, or cancer of the cervix and its precursor lesions ("high-risk types"), such as hpv-16. the transforming processes induced by these viruses depend on the proteins e5, e6, and e7. among these oncoproteins, the e6 protein stands out because it supports a particularly large number of functions and interactions with cel ...200314675634
roles of the e6 and e7 proteins in the life cycle of low-risk human papillomavirus type 11.many important functions have been attributed to the high-risk human papillomavirus (hpv) e6 and e7 proteins, including binding and degradation of p53 as well as interacting with rb proteins. in contrast, the physiological roles of the low-risk e6 and e7 proteins remain unclear. previous studies demonstrated that the high-risk e6 and e7 proteins also play roles in the productive life cycle by facilitating the maintenance of viral episomes (j. t. thomas, w. g. hubert, m. n. ruesch, and l. a. laim ...200414963169
identification of peptides that inhibit the dna binding, trans-activator, and dna replication functions of the human papillomavirus type 11 e2 protein.peptide antagonists of the human papillomavirus type 11 (hpv-11) e2-dna association were identified using a filamentous bacteriophage random peptide library. synthetic peptides antagonized the e2-dna interaction, effectively blocked e2-mediated transcriptional activation of a reporter gene in cell culture, and inhibited e1-e2-mediated hpv-11 dna replication in vitro. these peptides may prove to be useful tools for characterizing e2 function and for exploring the effectiveness of e2-inhibitor-bas ...200414963172
kinetics of in vitro adsorption and entry of papillomavirus virions.there has been much incongruence in reports addressing the rate at which papillomaviruses enter cultured cells. we used a recently developed qrt-pcr assay (j. virol. methods 111 (2003) 135) to analyze the expression, adsorption, and entry kinetics of human papillomavirus type 11 (hpv-11) in multiple cell lines. parallel experiments with hpv-40 and cottontail rabbit papillomavirus (crpv) were also performed with biologically relevant lines. infection was determined by the expression of early tran ...200414967496
preclinical model to test human papillomavirus virus (hpv) capsid vaccines in vivo using infectious hpv/cottontail rabbit papillomavirus chimeric papillomavirus particles.a human papillomavirus (hpv) vaccine consisting of virus-like particles (vlps) was recently approved for human use. it is generally assumed that vlp vaccines protect by inducing type-specific neutralizing antibodies. preclinical animal models cannot be used to test for protection against hpv infections due to species restriction. we developed a model using chimeric hpv capsid/cottontail rabbit papillomavirus (crpv) genome particles to permit the direct testing of hpv vlp vaccines in rabbits. ani ...200617005666
a self-processing ribozyme cassette: utility against human papillomavirus 11 e6/e7 mrna and hepatitis b virus.we have been developing a self-processing triple-ribozyme cassette, which consists of two cis-acting hammerhead ribozymes flanking an internal, trans-acting hammerhead ribozyme (itrz). here, the single itrz was replaced by two contiguous itrz (ditrz), and a short poly(a) tail was designed onto the 3' end of the liberated ditrz, to produce the "snip(aa)" cassette. self-processing of the cassette appeared to proceed efficiently in cells: the only region of the cassette identified in cells was the ...200415093190
failure of gamma interferon but not interleukin-10 expression in response to human papillomavirus type 11 e6 protein in respiratory papillomatosis.recurrent respiratory papillomatosis (rrp) is a chronic, debilitating disease of the upper airway caused by human papillomavirus type 6 (hpv-6) or hpv-11. we describe responses of peripheral blood mononuclear cells (pbmc) and t cells from rrp patients and controls to the hpv-11 early proteins e6 and e7. pbmc were exposed in vitro to purified e6 or e7 proteins or transduced with fusion proteins containing the first 11 amino acids of the human immunodeficiency virus type 1 protein tat fused to e6 ...200415138179
dose-ranging studies of the safety and immunogenicity of human papillomavirus type 11 and type 16 virus-like particle candidate vaccines in young healthy women.two candidate vaccines to prevent infection with human papillomavirus (hpv) types 11 and 16 were studied in similar double-blind, placebo-controlled, dose-escalation trials. l1 virus-like particle (vlp) vaccines were made from recombinant l1 capsid protein of hpv11 or hpv16. participants received 10, 20, 50, or 100 microg of hpv11 l1 vlps, 10, 40, or 80 microg of hpv16 l1 vlps, or placebo at months 0, 2, and 6. serum geometric mean antibody levels at month 7 were 258, 644, 647, and 1112 milli-me ...200415246631
integration of human papillomavirus type 11 in recurrent respiratory papilloma-associated cancer.the main objective was to demonstrate that human papillomavirus (hpv) type 11 is an aggressive virus that plays a significant role in the development of laryngeal cancer in patients with a history of recurrent respiratory papillomatosis (rrp). we have done so by preliminary investigation into the molecular mechanism underlying the malignant transformation of rrp to invasive squamous cell carcinoma.200415510012
recurrent respiratory papillomatosis: a longitudinal study comparing severity associated with human papilloma viral types 6 and 11 and other risk factors in a large pediatric population.a database was developed for prospective, longitudinal study of recurrent respiratory papillomatosis (rrp) in a large population of pediatric patients. data recorded for each patient included epidemiological factors, human papilloma virus (hpv) type, clinical course, staged severity of disease at each surgical intervention, and frequency of surgical intervention. the study hypothesizes that patients with hpv type 11 (hpv-11) and patients younger than 3 years of age at diagnosis are at risk for m ...200415514560
disseminated human papillomavirus type 11 infection in a patient with pemphigus vulgaris: confirmed by dna analysis.depending on the type of epithelium infected, human papillomaviruses (hpvs) are often subclassified as "cutaneous" or "mucosal" types of hpv. hpv type 11 is a mucosal type of virus and infects the genital tract or larynx. disseminated hpv-11 infection involving multiple body sites in cases of pemphigus vulgaris (pv) has not been reported. we report here an unusual case of severe pemphigus vulgaris associated with disseminated hpv-11 infection on the arms, hands, axillae, chest, abdomen, and both ...200415577767
hla class ii polymorphisms and susceptibility to recurrent respiratory papillomatosis.recurrent respiratory papillomatosis (rrp) is characterised by multiple laryngeal papillomas. left untreated, the lesions enlarge, spread, and endanger the airway. medical treatments are unsatisfactory, and repeated surgery remains the mainstay of therapy. rrp is caused by human papillomavirus (hpv) infection. however, since oral hpv infection is common and rrp is rare, other host and/or viral factors may contribute to pathogenesis. in an attempt to identify such factors, we have investigated 60 ...200312525627
hpv vaccine medimmune/glaxosmithkline.medimmune, in collaboration with glaxosmithkline, is developing a vaccine consisting of self-assembling, virus-like particles for the prevention of human papillomavirus (hpv) infection of the genital tract and associated cervical cancer. the vaccine candidates include the prototype vaccine, medi-501 (a vaccine directed against hpv-11), medi-503 (directed against hpv-16) and medi-504 (directed against hpv-18). following phase i studies, the hpv-16 and hpv-18 components were combined into a multiv ...200312669384
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
characterization of the minimal dna binding domain of the human papillomavirus e1 helicase: fluorescence anisotropy studies and characterization of a dimerization-defective mutant protein.the e1 helicase of papillomaviruses is required for replication of the viral double-stranded dna genome, in conjunction with cellular factors. dna replication is initiated at the viral origin by the assembly of e1 monomers into oligomeric complexes that have unwinding activity. in vivo, this process is catalyzed by the viral e2 protein, which recruits e1 specifically at the origin. for bovine papillomavirus (bpv) e1 a minimal dna-binding domain (dbd) has been identified n-terminal to the enzymat ...200312692220
[prokaryotic expression and purification of human papillomavirus type 11 l2e7 fusion protein vaccine and its immunnogenicity].to construct the escherichia coli (e. coli) prokaryotic expression system pet9ahpv11l2e7, purify the fusion protein l2e7 and study the immunnogenicity of the protein.200717653322
condyloma acuminatum and human papilloma virus infection in the oral mucosa of children.the purpose of this study was to investigate the clinicopathological features of oral condylomas in children and condylomatous lesions of their mothers. moreover, the authors sought to determine the mode of transmission of this disease and to find the genotype of human papilloma virus (hpv) in the children's oral condyloma.200312723841
the human papillomavirus type 11 e1--e4 protein is a transglutaminase 3 substrate and induces abnormalities of the cornified cell envelope.the human papillomavirus (hpv) e1--e4 protein is detected in the cytoplasm of differentiated keratinocytes, near the cornified cell envelope. hpv does not induce lysis of the infected keratinocyte, and the normally durable cornified cell envelope that forms during keratinocyte differentiation would seemingly inhibit viral egress. hpv infection induces abnormalities of the cornified cell envelope, but the exact mechanisms involved are not well understood. we tested whether the hpv 11 e1--e4 prote ...200616257432
ccaat/enhancer-binding protein beta represses human papillomavirus 11 upstream regulatory region expression through a promoter-proximal yy1-binding site.ccaat/enhancer-binding protein beta (c/ebpbeta) can function as a repressor or as an activator of human papillomavirus (hpv) gene expression, depending on which cell type the experiments are conducted. in this report, it was shown that within primary human foreskin keratinocyte cells (hfk) the activity of c/ebpbeta can be switched from that of a repressor of hpv11 expression to an activator by mutating a single promoter-proximal consensus yy1-binding site within the hpv11 upstream regulatory reg ...200616361417
[study on the genotyping of human papillomavirus using a new dna liquid chip in women of high-risk group of shandong province].to evaluate the diagnostic applicability of human papillomavirus (hpv) liquid chip assay which is based on luminex xmap system, and perform a hpv epidemiologic study with the liquid chip in women of shandong province.200717877181
sexually transmitted infections, blood-borne viruses and risk behaviour in an australian senior high school population--the shlirp study.to determine the feasibility and acceptability of screening for sexually transmitted infections and blood-borne viruses and to study the profile of sexual activity and other risk behaviours in a senior high school population.200516402670
high incidence of malignant transformation of laryngeal papilloma in taiwan.papillomas of the larynx include solitary laryngeal papilloma and recurrent respiratory papillomatosis. this study investigated the incidence of malignant transformation and assessed possible risk factors for laryngeal papillomas.200817975511
dynamic localization of the human papillomavirus type 11 origin binding protein e2 through mitosis while in association with the spindle apparatus.papillomaviral dna replicates as extrachromosomal plasmids in squamous epithelium. viral dna must segregate equitably into daughter cells to persist in dividing basal/parabasal cells. we have previously reported that the viral origin binding protein e2 of human papillomavirus types 11 (hpv-11), 16, and 18 colocalized with the mitotic spindles. in this study, we show the localization of the hpv-11 e2 protein to be dynamic. it colocalized with the mitotic spindles during prophase and metaphase. at ...200616641272
the human papillomavirus type 11 e1/\e4 protein is not essential for viral genome amplification.an abundant human papillomavirus (hpv) protein e1/\e4 is expressed late in the virus life cycle in the terminally differentiated layers of epithelia. the expression of e1/\e4 usually coincides with the onset of viral dna amplification. however, the function of e1/\e4 in viral life cycle is not completely understood. to examine the role of e1/\e4 in the virus life cycle, we introduced a single nucleotide change in the hpv-11 genome to result in a truncation of e1/\e4 protein without affecting the ...200616687161
more men than women make mucosal iga antibodies to human papillomavirus type 16 (hpv-16) and hpv-18: a study of oral hpv and oral hpv antibodies in a normal healthy population.we have previously shown the high prevalence of oral anti-human papillomavirus type 16 (hpv-16) antibodies in women with hpv-associated cervical neoplasia. it was postulated that the hpv antibodies were initiated after hpv antigenic stimulation at the cervix via the common mucosal immune system. the present study aimed to further evaluate the effectiveness of oral fluid testing for detecting the mucosal humoral response to hpv infection and to advance our limited understanding of the immune resp ...200616762074
presence of human papillomavirus dna in tonsillectomy specimens.the objectives of this prospective case-control study were to study the prevalence of human papillomavirus (hpv) in tonsillectomy specimens from pediatric patients without recurrent respiratory papillomatosis (rrp), and to study methods of hpv detection.200616885738
brd4 links chromatin targeting to hpv transcriptional silencing.the e2 protein encoded by human papillomaviruses (hpvs) inhibits expression of the viral e6 oncoprotein, which, in turn, regulates p53 target gene transcription. to identify cellular proteins involved in e2-mediated transcriptional repression, we isolated an e2 complex from human cells conditionally expressing hpv-11 e2. surprisingly, the double bromodomain-containing protein brd4, which is implicated in cell cycle control and viral genome segregation, was found associated with e2 and conferred ...200616921027
association of e6ap (ube3a) with human papillomavirus type 11 e6 protein.the cellular e3 ubiquitin ligase e6ap (ube3a) interacts with the cancer-associated hpv e6 oncoproteins, where together with the viral e6 oncoprotein it binds and targets the degradation of the p53 tumor suppressor. we find that the hpv-11e6 protein also associates with e6ap in vivo, and thereby can target the degradation of an e6-associated protein. mutation of an e6-binding lxxll peptide motif on e6ap eliminated the association, revealing a common mode of interaction between high- and low-risk ...200717023019
human papilloma virus in hyperplastic tonsillar and adenoid tissues in children.human papillomavirus (hpv) in childhood causes skin and anogenital warts as well as the recurrent respiratory papillomatosis, a life-threatening cause of upper airway obstruction in children. to date, the information on hpv infection in tonsillar and adenoid hyperplasia in children is limited.200617133162
conjunctival condylomata acuminata.to report a case of sexually transmitted conjunctival squamous papillomas and to propose a new term for this condition.200818520518
an inhibitor of the epidermal growth factor receptor function does not affect the ability of human papillomavirus 11 to form warts in the xenografted immunodeficient mouse model.epidermal growth factor receptor (egfr) has been shown to be induced and activated in cells infected with hpv, suggesting that it may play a physiological role in viral replication or in the formation or maintenance of warts. to investigate this possibility, human foreskin tissue was infected with hpv11 and transplanted onto the renal capsule and the dermis of immunodeficient mice. the animals were treated orally or topically with the potent egfr inhibitor cp-545130, with treatment starting eith ...200717239450
optimization and determination of the absolute configuration of a series of potent inhibitors of human papillomavirus type-11 e1-e2 protein-protein interaction: a combined medicinal chemistry, nmr and computational chemistry approach.we have previously reported the discovery and initial sar optimization of the first series of inhibitors of the human papillomavirus type-11 (hpv11) e1-e2 protein-protein interaction. these inhibitors featured an indandione system spiro-fused onto an all syn substituted tetrahydrofuran ring. in this paper, we report new sar efforts which have led to the identification of the first low nanomolar inhibitor of the hpv11 e1-e2 protein-protein interaction. in addition, we report a combined nmr and co ...200717306550
oral inverted ductal papilloma associated with condyloma acuminata and hpv in an hiv+ patient.oral inverted ductal papillomas are rare benign tumours of minor salivary glands. a case that appeared in a middle-aged hiv+ woman simultaneous to two condyloma acuminata on the lips is described. the presence of human papilloma virus (hpv) 11 dna was demonstrated in all the samples using polymerase chain reaction. hpv could play an important role in the aetiology and pathogenesis of these lesions in this patient.200818774261
codon optimization of the human papillomavirus 11 (hpv 11) l1 gene leads to increased gene expression and formation of virus-like particles in mammalian epithelial cells.the 505 amino acid l1 protein of the human papillomavirus type 11 (hpv 11) is the major capsid polypeptide that has been shown to self-assemble into virus-like particles (vlps) in vivo and in vitro. while l1 is essential for viral infection, expression studies in mammalian cells have been hampered by different codon preference between the virus and its host. to optimize l1 gene expression in mammalian cells, we converted wild-type hpv 11 l1 (11 l1wt) codons to those more common in human genes. t ...200415262495
hpv dna frequency and subset analysis in human breast cancer patients' normal and tumoral tissue samples.viruses are known to be associated with human malignancies, e.g., epstein-barr virus, human papillomavirus (hpv) and human t-cell leukemia virus type i. we conducted a prospective study to define the role of hpv in breast cancer. the malignant and normal breast tissue samples of 50 consecutive breast cancer patients were obtained postoperatively. dna extracted from all tissues was amplified with the polymerase chain reaction using hpv primers. hpv 11, 16, 18, 33 subtypes were searched in hpv-dna ...200617310842
presence of papillomavirus sequences in condylomatous lesions of the mamillae and in invasive carcinoma of the breast.viruses including epstein-barr virus (ebv), a human equivalent of murine mammary tumour virus (mmtv) and human papillomavirus (hpv) have been implicated in the aetiology of human breast cancer. we report the presence of hpv dna sequences in areolar tissue and tumour tissue samples from female patients with breast carcinoma. the presence of virus in the areolar-nipple complex suggests to us a potential pathogenic mechanism.200415642157
human papillomavirus dna detection and typing in male urine samples from a high-risk population from argentina.the aim of the present study was to evaluate the first void urine (fvu) as a non-invasive sampling method for hpv detection and genotyping in a high-risk population. men presenting with hpv associated penile lesions or hpv positive partners attending a urological department in la plata, argentina were enrolled for hpv detection and genotyping. dna from 185 first-void urine samples was evaluated for the presence of hpv by nested polymerase chain reaction using my09/11 and gp05/06 primers. the vir ...200415664072
transitional cell neoplasm of the nasolacrimal duct associated with human papillomavirus type 11.tumors of the lacrimal sac are rare but noteworthy because of their significant potential to become malignant or life-threatening if treatment is delayed. dermatologists may be the first to encounter such neoplasms.201019615034
metachronous squamous cell carcinomas evolving from independent oropharyngeal and pulmonary squamous papillomas: association with human papillomavirus 11 and lack of aberrant p53, rb, and p16 protein expression.squamous cell carcinoma evolving from squamous papilloma in both the upper and lower respiratory tract in the same patient is uncommon. the molecular mechanisms underlying the progression have not been well investigated. we herein describe a case of squamous cell carcinoma arising from respiratory papilloma in two independent occasions. the patient initially had oropharyngeal squamous cell carcinoma arising in a squamous papilloma at the age of 25 years. he subsequently developed squamous cell c ...200415668901
factors influencing subcellular localization of the human papillomavirus l2 minor structural protein.two structural proteins form the capsids of papillomaviruses. the major structural protein l1 is the structural determinant of the capsids and is present in 360 copies arranged in 72 pentamers. the minor structural protein l2 is estimated to be present in twelve copies per capsid. possible roles for l2 in interaction with cell surface receptors and in virion uptake have been suggested. as previously reported, l2 localizes in subnuclear domains identified as nuclear domain 10 (nd10). as it was de ...200616257028
expression of hpv-11 l1 protein in transgenic arabidopsis thaliana and nicotiana tabacum.we have investigated the possibility and feasibility of producing the hpv-11 l1 major capsid protein in transgenic arabidopsis thaliana ecotype columbia and nicotiana tabacum cv. xanthi as potential sources for an inexpensive subunit vaccine.200717850660
sexually transmitted infections, bacterial vaginosis, and candidiasis in women of reproductive age in rural northeast brazil: a population-based study.population-based data on sexually transmitted infections (sti), bacterial vaginosis (bv), and candidiasis reflect the epidemiological situation more accurately than studies performed in specific populations, but such data are scarce. to determine the prevalence of sti, bv, and candidiasis among women of reproductive age from a resource-poor community in northeast brazil, a population-based cross sectional study was undertaken. all women from seven hamlets and the centre of pacoti municipality in ...200717924006
e6 and e7 oncogene expression by human papilloma virus (hpv) and the aggressive behavior of recurrent laryngeal papillomatosis (rlp).recurrent laryngeal papillomatosis (rlp), a chronic disease associated with human papilloma virus (hpv), requires serial surgical procedures for debulking, resulting in debilitating long-term dysphonia, laryngeal scarring, and rarely malignant degeneration. human papilloma virus 11 tumors have been widely accepted as more aggressive than hpv 6 tumors; however, the clinical course has been difficult to predict at disease onset, and the biologic mediators of proliferation have not been well charac ...200817990904
remodeling of the human papillomavirus type 11 replication origin into discrete nucleoprotein particles and looped structures by the e2 protein.the human papillomavirus (hpv) dna replication origin (ori) shares a common theme with many dna control elements in having multiple binding sites for one or more proteins spaced over several hundreds of base pairs. the hpv type 11 ori spans 103 bp and contains three palindromic e2 binding sites (e2bs-2, e2bs-3, and e2bs-4) for the dimeric e2 ori binding protein. these sites are separated by 64 and 3 bp. e2bs-1 is located 288 bp upstream of e2bs-2 and is not required for efficient transient or ce ...200818067922
[construction and immunogenicity evaluation of chimerical dna vaccine of human papillomavirus type 11].to construct chimerical dna vaccine plasmid of human papillomavirus type 11 (hpv11) l1-e7, and to evaluate its immunogenicity.200920104772
[expression, purification and immunogenicity of human papillomavirus type 11 virus-like particles from escherichia coli].to produce human papillomavirus type 11 virus-like particles (hpv11 vlps) from escherichia coli and to investigate its immunogenicity and type cross neutralization nature.200920112683
seroepidemiology of human papillomavirus type 11 in the united states: results from the third national health and nutrition examination survey, 1991--1994.the national seroprevalence of the nononcogenic human papillomavirus (hpv) type 11, one of the types targeted by the quadrivalent hpv vaccine, has not been evaluated in the united states. the objectives of this study were to estimate the national seroprevalence and evaluate predictors of hpv-11 seropositivity.200818091027
prevalence of bk virus and human papillomavirus in human prostate cancer.polyomaviruses such as the bk virus (bkv), jc virus (jcv) and sv40, as well as the human papillomaviruses (hpv) are frequently detected throughout human populations, causing subclinical persistent infections and inducing oncogenesis in human and other cell lines. to test the involvement of these viruses in prostate tumorigenesis, we investigated the prevalence of bkv, jcv and hpv in a series of human prostatic malignancies. forty-two samples of diagnosed prostatic malignancies were tested using ...200718161654
the l2 minor capsid protein of low-risk human papillomavirus type 11 interacts with host nuclear import receptors and viral dna.analysis of the interactions of low-risk human papillomavirus type 11 (hpv11) l2 with karyopherin beta (kap beta) nuclear import receptors revealed that l2 interacted with kap beta 1, kap beta 2, and kap beta 3 and formed a complex with the kap alpha 2 beta 1 heterodimer. hpv11 l2 contains two nuclear localization signals (nlss)-in the n terminus and the c terminus-that could mediate its nuclear import via a classical pathway. each nls was functional in vivo, and deletion of both of them abolish ...200616873281
safety and immunogenicity of co-administered quadrivalent human papillomavirus (hpv)-6/11/16/18 l1 virus-like particle (vlp) and hepatitis b (hbv) vaccines.adolescents and young adults are at high risk for human papillomavirus (hpv) and hepatitis b virus (hbv) infections, which are preventable by currently available, safe and effective, prophylactic vaccines. however, development of a combined immunization strategy may lead to better compliance for these vaccines, thereby contributing to the overall goal of protection against these diseases. this study assessed the safety and immunogenicity of co-administered quadrivalent hpv-6/11/16/18 l1 vlp and ...200818164106
possible role for cellular karyopherins in regulating polyomavirus and papillomavirus capsid assembly.polyomavirus and papillomavirus (papovavirus) capsids are composed of 72 capsomeres of their major capsid proteins, vp1 and l1, respectively. after translation in the cytoplasm, l1 and vp1 pentamerize into capsomeres and are then imported into the nucleus using the cellular alpha and beta karyopherins. virion assembly only occurs in the nucleus, and cellular mechanisms exist to prevent premature capsid assembly in the cytosol. we have identified the karyopherin family of nuclear import factors a ...200818701594
[vaccine against human papilloma virus].genital human papilloma virus infection (hpv) is the most common sexually transmitted infection worldwide, it is the cause of genital warts, and it is related with cervical cancer, the second most common cause of death from cancer in women in america, and the first in underdeveloped countries, and it is related with penis and prostate cancer in males also, and with anal cancer in both genders. this review examines the most important actual facts about hpv infection, and the new prophylactic vacc ...200819263667
mitogen-activated protein kinases activate the nuclear localization sequence of human papillomavirus type 11 e1 dna helicase to promote efficient nuclear import.human and animal papillomavirus dna replicates as multicopy nuclear plasmids. replication requires two viral proteins, the origin-recognition protein e2 and the replicative dna helicase e1. using genetic, biochemical, and immunofluorescence assays, we demonstrated that efficient nuclear import of the human papillomavirus (hpv) type 11 e1 protein depends on a codominant bipartite nuclear localization sequence (nls) and on phosphorylation of the serine residues s89 and s93 by the mitogen-activated ...200717344281
incidence and duration of cervical human papillomavirus 6, 11, 16, and 18 infections in young women: an evaluation from multiple analytic perspectives.to estimate the incidence and duration of cervical human papillomavirus (hpv)-6, hpv-11, hpv-16, and hpv-18 infections in a population of young american women.200717416761
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