Construction of a vector for inducible ectopic expression of the Epstein-Barr virus LMP1 protein to study oncoviral properties in human cells cultured in vitro

• Grant number: 24/00937-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2024
• End date: May 31, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Deilson Elgui de Oliveira
• Grantee: Anderson Valim Pereira
• Host Institution: Instituto de Biotecnologia (IBTEC). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Cancers are a global health concern, with significant impacts in terms of morbidity and mortality, particularly in older adults. Population ageing and the high prevalence of unhealthy lifestyle habits have led to expectations of an increase in the incidence of cancers worldwide. Some human cancers are associated with infectious agents, particularly the diseases most prevalent in developing countries. Among the infectious agents known to be carcinogenic to humans is the Epstein-Barr Virus (EBV), which latently infects more than 90% of the adult population and whose infection contributes to the pathogenesis of various human cancers, particularly the endemic form of Burkitt's lymphoma and the undifferentiated form of nasopharyngeal carcinoma. This work aims to develop recombinant vectors for the regulated expression of the EBV LMP1 protein in human cells grown in vitro, in order to further the study of the oncogenic properties of this viral product. Constructs for the inducible expression of LMP1 from the Akata and M81 EBV genotypes will be generated using cloning techniques. Once validated, the constructs will be used to establish experimental models based on tetracycline-inducible expression of EBV LMP1 in a dose-dependent manner. At the end of this project, it is hoped that the vectors for inducible expression of EBV LMP1 will have been validated in structural and functional terms, so that they can be used to investigate the impacts and molecular mechanisms of viral oncoprotein activity under different experimental conditions. This tool could contribute to elucidating the pathogenesis of EBV-associated cancers, allowing the identification of molecular targets for strategies based on inhibiting these properties for the treatment of virus-associated cancers.