Oropouche virus pathogenesis: Functions of non-structural proteins of the medium (NSm) and small segments (NSs).

• Grant number: 24/10555-4
• Support Opportunities: Scholarships in Brazil - Master
• Start date: December 01, 2024
• End date: March 31, 2026
• Field of knowledge: Biological Sciences - Microbiology
• Principal Investigator: Eurico de Arruda Neto
• Grantee: Tufi Antonio Nasser Neto
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 19/26119-0 - Emerging and re-emerging viruses: biology, pathogenesis and prospection, AP.TEM

Abstract

The Oropouche virus (OROV) is a human pathogen transmitted by arthropods and widely distributed in tropical regions such as Central and South America, mainly present in the Amazon region. The OROV genome consists of three RNA strands named L, M, and S, where M and S encode the non-structural proteins NSm and NSs, respectively. Since the initial identification of the virus, a large number of cases are reported annually, with OROV being the second leading cause of arbovirus fever in Brazil, where there are reports that the virus can cause systemic infections leading to severe complications. Nevertheless, studies on the role of non-structural proteins in OROV pathogenesis are limited. Therefore, the current project aims to fill this gap. Previous studies from our group have shown that the non-structural protein NSm participates in viral replication, enhancing its efficiency, and that the NSs protein mainly contributes to triggering apoptosis. Literature data indicate pronounced tropism of OROV for the liver, raising transaminase levels, and also affecting the CNS, mainly the brain, where it can cause meningoencephalitis and cerebral edema. Based on this context, the present study aims to conduct a comparative analysis of the viral pathogenesis of OROV WT and the mutants ”NSm, ”NSs, and ”NSm/NSs in BALB/c mice using a standardized experimental model in our laboratory.