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Analysis of HPV-18 transcriptional activity during cell differentiation

Grant number: 16/16528-2
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): March 01, 2017
Status:Discontinued
Field of knowledge:Biological Sciences - Biochemistry - Biochemistry of Microorganisms
Principal Investigator:Laura Cristina Sichero Vettorazzo
Grantee:Aline Lopes Ribeiro
Home Institution: Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira (ICESP). Coordenadoria de Serviços de Saúde (CSS). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Associated scholarship(s):19/25486-0 - The role of EVER1/2 upon Beta-HPV transcriptional activity, BE.EP.DR

Abstract

Human papillomavirus (HPV) type most worldwide prevalent in pre-invasive tumors and in invasive carcinomas of the cervix is the HPV-16 , followed by HPV-18. However, HPV-18 predominates in adenocarcinomas (56%) and adenosquamous tumors (39% ). Several evidences indicate that synchronization of the virus life cycle by epithelial differentiation program, in addition to epitheliotropism, is partly due to the composition of transcription factor binding sites (TFs) to the long control region (LCR) and differential expression of these factors, or co-factors, necessary for transcription, not only on epithelial cells but also through the different layers of stratified epithelium. Until this moment, very little progress has been made about the HPV-18 gene expression in the context of different stages of the viral life cycle. For these reason, this project aims to comprehensively characterize the transcriptional activity of the main early promoter of HPV-18 (P105) under conditions representing the different stages of the viral life cycle. More specifically, the purpose is to: (1) evaluate the HPV-18 transcriptional activity of P105 in keratinocytes undifferentiated and differentiated; (2) to analyze the levels of 345 TFs expressed in undifferentiated and differentiated keratinocytes; (3) determine which of these cell TFs bind to the HPV-18 LCR; (4) determine the impact of these individually and synergistically factors on HPV-18 transcriptional activity of P105. This knowledge is essential to better understand the biology, pathogenesis, diagnosis and clinical management of diseases associated with this virus type. (AU)