Differences in transcriptional activity of human papillomavirus type 6 molecular variants in recurrent respiratory papillomatosis

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dc.contributor.authorBonfim, Caroline Measso do [UNESP]
dc.contributor.authorSimão Sobrinho, João
dc.contributor.authorNogueira, Rodrigo Lacerda
dc.contributor.authorKupper, Daniel Salgado
dc.contributor.authorValera, Fabiana Cardoso Pereira
dc.contributor.authorNogueira, Maurício Lacerda
dc.contributor.authorVilla, Luisa Lina
dc.contributor.authorRahal, Paula [UNESP]
dc.contributor.authorSichero, Laura
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionInstituto do Câncer do Estado de São Paulo
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionFaculdade de Medicina de São José do Rio Preto (FAMERP)
dc.date.accessioned2015-12-07T15:35:13Z
dc.date.available2015-12-07T15:35:13Z
dc.date.issued2015
dc.description.abstractA significant proportion of recurrent respiratory papillomatosis (RRP) is caused by human papillomavirus type 6 (HPV-6). The long control region (LCR) contains cis-elements for regulation of transcription. Our aim was to characterize LCR HPV-6 variants in RRP cases, compare promoter activity of these isolates and search for cellular transcription factors (TFs) that could explain the differences observed. The complete LCR from 13 RRP was analyzed. Transcriptional activity of 5 variants was compared using luciferase assays. Differences in putative TFs binding sites among variants were revealed using the TRANSFAC database. Chromatin immunoprecipation (CHIP) and luciferase assays were used to evaluate TF binding and impact upon transcription, respectively. Juvenile-onset RRP cases harbored exclusively HPV-6vc related variants, whereas among adult-onset cases HPV-6a variants were more prevalent. The HPV-6vc reference was more transcriptionally active than the HPV-6a reference. Active FOXA1, ELF1 and GATA1 binding sites overlap variable nucleotide positions among isolates and influenced LCR activity. Furthermore, our results support a crucial role for ELF1 on transcriptional downregulation. We identified TFs implicated in the regulation of HPV-6 early gene expression. Many of these factors are mutated in cancer or are putative cancer biomarkers, and must be further studied.en
dc.description.affiliationLaboratory of Genomic Studies, Universidade do Estado de São Paulo, UNESP, São José do Rio Preto, SP, Brazil
dc.description.affiliationMolecular Biology Laboratory, Center of Translational Oncology, Instituto do Câncer do Estado de São Paulo, ICESP, São Paulo, Brazil
dc.description.affiliationDepartment of Ophthalmology/Otorhinolaryngology and Head/Neck Surgery, Discipline Otorhinolaryngology, Faculty of Medicine of Ribeirão Preto, Universidade de São Paulo, USP, São Paulo, Brazil
dc.description.affiliationLaboratory of Research in Virology, Faculty of Medicine of São José do Rio Preto, FAMERP, São José do Rio Preto, Brazil
dc.description.affiliationMolecular Biology Laboratory, Center of Translational Oncology, Instituto do Câncer do Estado de São Paulo, ICESP, São Paulo, Brazil
dc.description.affiliationDepartment of Radiology and Oncology, School of Medicine, Universidade de São Paulo, USP, São Paulo, Brazil
dc.description.affiliationSchool of Medicine, Santa Casa de São Paulo and HPV Institute, São Paulo, Brazil
dc.description.affiliationUnespLaboratory of Genomic Studies, Universidade do Estado de São Paulo, UNESP, São José do Rio Preto, SP, Brazil
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tencnológico (CNPq)
dc.description.sponsorshipIdFAPESP: 2010/00029-0
dc.description.sponsorshipIdFAPESP: 2008/57889-1
dc.description.sponsorshipIdCNPq: 573799/2008-3
dc.identifierhttp://dx.doi.org/10.1371/journal.pone.0132325
dc.identifier.citationPlos One, v. 10, n. 7, 2015.
dc.identifier.doi10.1371/journal.pone.0132325
dc.identifier.filePMC4494706.pdf
dc.identifier.issn1932-6203
dc.identifier.lattes7991082362671212
dc.identifier.orcid0000-0001-5693-6148
dc.identifier.pmcPMC4494706
dc.identifier.pubmed26151558
dc.identifier.urihttp://hdl.handle.net/11449/131421
dc.language.isoeng
dc.publisherPublic Library Science
dc.relation.ispartofPlos One
dc.relation.ispartofjcr2.766
dc.relation.ispartofsjr1,164
dc.rights.accessRightsAcesso aberto
dc.sourcePubMed
dc.titleDifferences in transcriptional activity of human papillomavirus type 6 molecular variants in recurrent respiratory papillomatosisen
dc.typeArtigo
dcterms.rightsHolderPublic Library Science
unesp.author.lattes7991082362671212[8]
unesp.author.orcid0000-0001-5693-6148[8]
unesp.campusUniversidade Estadual Paulista (Unesp), Instituto de Biociências Letras e Ciências Exatas, São José do Rio Pretopt

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