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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 2015-07, Vol.10 (7), p.e0132325-e0132325
Main Authors: Measso do Bonfim, Caroline, Simão Sobrinho, João, Lacerda Nogueira, Rodrigo, Salgado Kupper, Daniel, Cardoso Pereira Valera, Fabiana, Lacerda Nogueira, Maurício, Villa, Luisa Lina, Rahal, Paula, Sichero, Laura
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cited_by cdi_FETCH-LOGICAL-c692t-58f36710dd9e7ae7539518cf7154442e78cb7aab073e8d14a70bf193ccbeba8a3
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creator Measso do Bonfim, Caroline
Simão Sobrinho, João
Lacerda Nogueira, Rodrigo
Salgado Kupper, Daniel
Cardoso Pereira Valera, Fabiana
Lacerda Nogueira, Maurício
Villa, Luisa Lina
Rahal, Paula
Sichero, Laura
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.
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subjects Age
Analysis
Base Sequence
Binding sites
Biomarkers
Cancer
Cell Line
Chromatin
Cloning
Deoxyribonucleic acid
Discipline
DNA
GATA-1 protein
Gene expression
Gene regulation
Genetic aspects
Genetic transcription
Genetic Variation
Genomes
Human papillomavirus
Human papillomavirus 6 - genetics
Humans
Laboratories
Luciferase
Medicine
Molecular biology
Molecular Sequence Data
Oncology
Otolaryngology
Papilloma
Papillomavirus infections
Papillomavirus Infections - genetics
Papillomavirus Infections - virology
Papillomaviruses
Plasmids
Promoter Regions, Genetic
Protein Binding
Respiratory Tract Infections - genetics
Respiratory Tract Infections - virology
Surgery
Transcription factors
Transcription Factors - metabolism
Transcription, Genetic
title Differences in Transcriptional Activity of Human Papillomavirus Type 6 Molecular Variants in Recurrent Respiratory Papillomatosis
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