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Effects of Epstein-Barr protein RPMS1 expression in human cells cultured in vitro

Grant number: 18/12164-1
Support type:Scholarships in Brazil - Master
Effective date (Start): October 01, 2018
Status:Discontinued
Field of knowledge:Health Sciences - Medicine
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Deilson Elgui de Oliveira
Grantee:Beatrice Adrianne Silva Jorge
Home Institution: Instituto de Biotecnologia (IBTEC). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
Associated scholarship(s):19/05061-4 - Effects of Epstein-Barr virus RPMS1 protein expression on lymphoid human cells cultured in vitro, BE.EP.MS

Abstract

The Epstein-Barr virus (EBV) - formally human gammaherpesvirus 4 (HHV-4) - is a herpesvirus associated with the development of a variety of human malignancies, notably Burkitt lymphoma (BL) and nasopharyngeal carcinoma (NPC), but also subsets of cases for Hodgkin and non-Hodgkin lymphomas (particularly in immunocompromised patients) and gastric carcinomas. The viral genome is detected in neoplastic cells in virtually all cases of undifferentiated NPC, an aggressive cancer endemic in Asia and in some regions of North Africa. Besides EBV infection, other factors contribute to the etiopathogenesis of the NPC, such as the individual genetic background and cultural habits, such as consumption of Chinese-style salty fish and the use of some plants in traditional medicine. The oncogenic potential of EBV is associated with viral products that interfere with critical biological processes, such as genetic stability, apoptosis regulation, and immortalization capacity. So far, the main EBV oncogenic product is the latent protein membrane 1 (LMP1), which causes constitutive activation of NF-kB, among other activities. Nonetheless, other viral products only recently have been investigated, such as the EBV RPMS1 protein, which is generated by alternative splicing of of the BamHI A right transcripts (BART) segment of the viral genome. Although there is scarce data about the RPMS1 biological properties to date, this viral protein was reported to modulate the Notch pathway, and it may possibly contribute for the EBV-induced transformation of epithelial cells. Noteworthy, a A/G single nucleotide polymorphism (SNP) at position 155391 in the RPMS1 coding sequence was associated with increased risk for NPC, but the mechanisms for this association remains to be elucidated. Thus, this study aims to investigate the in vitro phenotypic features of cells expressing the 155391A and 155391G variants of EBV RPMS1. For this intent, lentiviral vectors for inducible expression of EBV RPMS1 will be generated and transduced in immortalized nasopharyngeal cells, which will be subsequently evaluated for cell viability, apoptosis, cell migration and cell invasion in vitro.