Construction of a retroviral vector for human TREX1 gene overexpression

• Grant number: 18/03993-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2018
• End date: May 31, 2019
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Enrique Mario Boccardo Pierulivo
• Grantee: Filipe de Moura Bragança
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Human papillomaviruses (HPV) that infect the cervix can be classified as low risk or high oncogenic risk. Infection with low-oncogenic risk HPV is associated with the development of benign papillomas and low-grade lesions with a low tendency for malignant progression, which are usually eliminated by the host immune system. However, high-risk HPVs have a high carcinogenic potential and are associated with the development of cervical cancer. In an earlier study from our laboratory it was observed that cell lines derived from HPV positive cervical tumors express high levels of the enzyme Three Prime Repair exonuclease I (TREX1) and that it silencing decreases the viability of these cells. In addition, using clinical samples we observed that the expression levels of this protein increase according to the severity of the disease. TREX1 is the main DNA exonuclease of the cytoplasm. This protein has been associated with repair of lesions in the DNA and control of viral infections by elimination of viral DNA from the cytoplasm and regulation of interferon-mediated signaling pathways. However, the role of TREX1 in the pathogenesis associated with HPV infection has not been studied. In the present project, we aim to construct a retroviral vector to overexpress the TREX1 gene in cells expressing HPV genes. This tool will allow the depth analysis of the role of this factor in the cellular transformation process associated with this virus. Key words: HPV, TREX1, retroviral vector, cervical cancer. (AU)