Differences in Transcriptional Activity of Human Papillomavirus Type 6 Molecular Variants in Recurrent Respiratory Papillomatosis
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 thes...
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Published in | PloS one Vol. 10; no. 7; p. e0132325 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Public Library of Science
07.07.2015
Public Library of Science (PLoS) |
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Competing Interests: LLV is a consultant of Merck Sharp & Dohme for HPV vaccines. None of the other authors have conflicts of interest to report. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials. Conceived and designed the experiments: CMdB LLV PR LS. Performed the experiments: CMdB JSS LS. Analyzed the data: CMdB JSS RLN DSK FCPV MLN LS. Contributed reagents/materials/analysis tools: CMdB JSS RLN DSK FCPV MLN LLV PR LS. Wrote the paper: CMdB LLV PR LS. |
ISSN: | 1932-6203 1932-6203 |
DOI: | 10.1371/journal.pone.0132325 |