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PLoS One. 2015 Jul 7;10(7):e0132325. doi: 10.1371/journal.pone.0132325. eCollection 2015.

Differences in Transcriptional Activity of Human Papillomavirus Type 6 Molecular Variants in Recurrent Respiratory Papillomatosis.

Author information

  • 1Laboratory of Genomic Studies, Universidade do Estado de São Paulo, UNESP, São José do Rio Preto, SP, Brazil.
  • 2Molecular Biology Laboratory, Center of Translational Oncology, Instituto do Câncer do Estado de São Paulo, ICESP, São Paulo, Brazil.
  • 3Department of Ophthalmology/Otorhinolaryngology and Head/Neck Surgery, Discipline Otorhinolaryngology, Faculty of Medicine of Ribeirão Preto, Universidade de São Paulo, USP, São Paulo, Brazil.
  • 4Laboratory of Research in Virology, Faculty of Medicine of São José do Rio Preto, FAMERP, São José do Rio Preto, Brazil.
  • 5Molecular Biology Laboratory, Center of Translational Oncology, Instituto do Câncer do Estado de São Paulo, ICESP, São Paulo, Brazil; Department of Radiology and Oncology, School of Medicine, Universidade de São Paulo, USP, São Paulo, Brazil; School of Medicine, Santa Casa de São Paulo and HPV Institute, São Paulo, Brazil.

Abstract

A 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.

PMID:
26151558
PMCID:
PMC4494706
DOI:
10.1371/journal.pone.0132325
[PubMed - indexed for MEDLINE]
Free PMC Article
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