Role of OROV non-structural proteins in its pathogenesis

Abstract

The Oropouche Arbovirus (OROV) is the causative agent of Oropouche fever, whose main urban vector is Culicoides from Pará, an endemic disease in the Amazon region and emerging in other regions of the country, with new cases being reported in the Northeast, Central-West, and Southeast. In the last 60 years, it has been responsible for more than half a million of cases in approximately 30 outbreaks. OROV belongs to the order Bunyavirales, family Peribunyaviridae, genus Orthobunyavirus, and it is a virus with a genome consisting of single-stranded RNA and negative polarity. The M (medium) and S (small) segments encode the non-structural proteins NSm and NSs, respectively, whose functions in the pathogenesis of the virus are not known. Therefore, the present project proposes the use of the Oropouche virus with the non-structural proteins deleted (OROV/NSm and OROV/NSs) and the observation of changes in infected cells and animal models in relation to the wild type virus (OROV/WT). The impacts of the deletion of proteins on the kinetics of viral replication, formation of viral factories, induction of apoptosis and other forms of cell death, and cell viability will be analyzed. All these experiments will be performed in HeLa cell cultures. In addition, the impact of NSm and NSs deletion on neuroinvasion, signs of disease, and survival of neonate mice infected via the epithelial route will be evaluated.(AU)