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...
Main Authors: | , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2015-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC4494706?pdf=render |
_version_ | 1818236702271995904 |
---|---|
author | Caroline Measso do Bonfim João Simão Sobrinho Rodrigo Lacerda Nogueira Daniel Salgado Kupper Fabiana Cardoso Pereira Valera Maurício Lacerda Nogueira Luisa Lina Villa Paula Rahal Laura Sichero |
author_facet | Caroline Measso do Bonfim João Simão Sobrinho Rodrigo Lacerda Nogueira Daniel Salgado Kupper Fabiana Cardoso Pereira Valera Maurício Lacerda Nogueira Luisa Lina Villa Paula Rahal Laura Sichero |
author_sort | Caroline Measso do Bonfim |
collection | DOAJ |
description | 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. |
first_indexed | 2024-12-12T12:14:04Z |
format | Article |
id | doaj.art-b89578202f9f415785d4152d308fd18b |
institution | Directory Open Access Journal |
issn | 1932-6203 |
language | English |
last_indexed | 2024-12-12T12:14:04Z |
publishDate | 2015-01-01 |
publisher | Public Library of Science (PLoS) |
record_format | Article |
series | PLoS ONE |
spelling | doaj.art-b89578202f9f415785d4152d308fd18b2022-12-22T00:24:49ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01107e013232510.1371/journal.pone.0132325Differences in Transcriptional Activity of Human Papillomavirus Type 6 Molecular Variants in Recurrent Respiratory Papillomatosis.Caroline Measso do BonfimJoão Simão SobrinhoRodrigo Lacerda NogueiraDaniel Salgado KupperFabiana Cardoso Pereira ValeraMaurício Lacerda NogueiraLuisa Lina VillaPaula RahalLaura SicheroA 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.http://europepmc.org/articles/PMC4494706?pdf=render |
spellingShingle | Caroline Measso do Bonfim João Simão Sobrinho Rodrigo Lacerda Nogueira Daniel Salgado Kupper Fabiana Cardoso Pereira Valera Maurício Lacerda Nogueira Luisa Lina Villa Paula Rahal Laura Sichero Differences in Transcriptional Activity of Human Papillomavirus Type 6 Molecular Variants in Recurrent Respiratory Papillomatosis. PLoS ONE |
title | Differences in Transcriptional Activity of Human Papillomavirus Type 6 Molecular Variants in Recurrent Respiratory Papillomatosis. |
title_full | Differences in Transcriptional Activity of Human Papillomavirus Type 6 Molecular Variants in Recurrent Respiratory Papillomatosis. |
title_fullStr | Differences in Transcriptional Activity of Human Papillomavirus Type 6 Molecular Variants in Recurrent Respiratory Papillomatosis. |
title_full_unstemmed | Differences in Transcriptional Activity of Human Papillomavirus Type 6 Molecular Variants in Recurrent Respiratory Papillomatosis. |
title_short | Differences in Transcriptional Activity of Human Papillomavirus Type 6 Molecular Variants in Recurrent Respiratory Papillomatosis. |
title_sort | differences in transcriptional activity of human papillomavirus type 6 molecular variants in recurrent respiratory papillomatosis |
url | http://europepmc.org/articles/PMC4494706?pdf=render |
work_keys_str_mv | AT carolinemeassodobonfim differencesintranscriptionalactivityofhumanpapillomavirustype6molecularvariantsinrecurrentrespiratorypapillomatosis AT joaosimaosobrinho differencesintranscriptionalactivityofhumanpapillomavirustype6molecularvariantsinrecurrentrespiratorypapillomatosis AT rodrigolacerdanogueira differencesintranscriptionalactivityofhumanpapillomavirustype6molecularvariantsinrecurrentrespiratorypapillomatosis AT danielsalgadokupper differencesintranscriptionalactivityofhumanpapillomavirustype6molecularvariantsinrecurrentrespiratorypapillomatosis AT fabianacardosopereiravalera differencesintranscriptionalactivityofhumanpapillomavirustype6molecularvariantsinrecurrentrespiratorypapillomatosis AT mauriciolacerdanogueira differencesintranscriptionalactivityofhumanpapillomavirustype6molecularvariantsinrecurrentrespiratorypapillomatosis AT luisalinavilla differencesintranscriptionalactivityofhumanpapillomavirustype6molecularvariantsinrecurrentrespiratorypapillomatosis AT paularahal differencesintranscriptionalactivityofhumanpapillomavirustype6molecularvariantsinrecurrentrespiratorypapillomatosis AT laurasichero differencesintranscriptionalactivityofhumanpapillomavirustype6molecularvariantsinrecurrentrespiratorypapillomatosis |