Reverse genetics for Oropouche virus: role of the non structural protein NSs in apoptosis induction and antagonism of Type I IFN.

• Grant number: 12/19473-3
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: February 01, 2013
• End date: February 10, 2015
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: Eurico de Arruda Neto
• Grantee: Gustavo Olszanski Acrani
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 13/02798-0 - Reverse genetics of Oropouche virus: generation of mutants with truncated and deleted non structural NSs protein, BE.EP.PD

Abstract

The Oropouche virus (OROV) is the second most frequent arboviral ilness in Brazil, with more than 0.5 million cases documented in the last 30 years. OROV occurs predominantly in the Amazon region, but has been isolated in the Southeast. Furthermore, deforestation and redistribution of insects increase the risk of spreading the virus to other areas. The pathogenesis of OROV infection is not completely known. It was recently demonstrated by the candidate that the virus induces apoptosis and that this effect requires the synthesis of viral proteins. Studies indicate that NSs non-structural proteins from other Bunyaviruses are important in the control of apoptosis and type I IFN antagonism. The proposed study aims to evaluate the role of Oropouche NSs protein in the induction of apoptosis, "shut-off" of protein synthesis and antagonism of IFN type I. To this end, we are proposing to produce an infectious clone of OROV by reverse genetics, one which will yield recombinant viruses with "knock-out" for the NSs protein, as well as recombinant viruses with different regions of this protein truncated, in order to study the role of the NSs protein in virus replication and its role in phatogenesis. This study is important for understanding the cell biology of OROV and characterize a probable pro-apoptotic protein of Bunyavirus.