Renal Pathogenesis in Experimental Infection by the Oropouche Virus.

• Grant number: 25/00853-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2025
• End date: June 30, 2026
• Field of knowledge: Biological Sciences - Microbiology
• Principal Investigator: Eurico de Arruda Neto
• Grantee: Lucas Yuji Gomes Itikawa
• 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 an arthropod-borne pathogen widely distributed in tropical regions, primarily in the Amazon region, where it has historically caused significant outbreaks of febrile illness. Starting in 2023, OROV infections were detected across Brazil, leading to an epidemic 200 times larger than previously recorded. Alongside its geographic spread, more severe cases were reported, including deaths, maternal-fetal infections, and congenital infections associated with miscarriages and malformations.This project aims to investigate renal pathogenesis in OROV infection, considering the identification of the virus in the urine of infected patients, suggesting kidney involvement. To achieve this, the detection of structural proteins-via western blot and immunohistochemistry-and viral nucleic acids-via RT-qPCR-will be associated with specific markers of acute kidney injury and tubular damage (NGAL and cytokeratins), inflammatory patterns (interleukins), and cell death pathways (caspases 1, 3, 8, and 9, and RIPK1, RIPK3, and MLKL).In addition to investigating the tropism and effects of the pathogen on the kidney, the study will gather data on the role of OROV non-structural proteins in this infection using OROV WT and mutant strains OROV ¿NSm, OROV ¿NSs, and OROV ¿NSm/NSs. Thus, the study seeks to characterize viral pathogenesis and the contribution of potential virulence and attenuation factors in the kidneys of neonatal BALB/c mice using an experimental OROV infection model standardized in our laboratory.