Análise da variabilidade genética e expressão de HPV em papilomatose de laringe

• Autor(a) principal: Bonfim, Caroline Measso do [UNESP]
• Data de Publicação: 2014
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Repositório Institucional da UNESP
• Texto Completo: http://hdl.handle.net/11449/122218
• topic: Virologia; Variação genética; Virus do papiloma; Virus; Doenças por papilomavírus; Doenças sexualmente transmissiveis; Virology

Recurrent respiratory papillomatosis (RRP) is a disease characterized by the formation of benign papillomas in the upper respiratory tract. Human Papillomavirus infection (HPV) is the main cause of the disease, particularly types 6 and 11 which are considered low-risk oncogenic HPV. The promoter region LCR (Long Control Region) contains cis-regulatory elements for cellular and viral transcription factors (TF) that control viral early gene expression and replication. Nucleotide alterations within the LCR may overlap TFs elements and impact upon the binding affinity, the transcriptional activity and ultimately on the clinical outcome associated to HPV infections. Our aim was to characterize molecular variants of HPV among individuals diagnosed with RRP and to analyze the impact of LCR nucleotide divergence upon viral early transcription. LCR sequencing of the HPV-6 positive samples revealed five genomic variants not previously described. Through computational analysis, we found that nucleotide changes detected overlapps potential binding sites for several transcription factors. HPV-6vc-related variant was the most prevalent among the samples analyzed (69.2%) and more prevalent in cases of juvenile papillomatosis. Concerning transcriptional activity, HPV-6vc-related variant is more active than HPV-6a molecular variant. Further, we observed that other alterations observed strongly impacts transcriptional activity indirectly measured by luciferase assays. To our knowledge, this is the first report describing differences in promoter activity among naturally occurring variants of HPV-6. Research in this area is anticipated to provide important information concerning the biological significance of HPV-6 intratype genomic variability