Study of the influence of Oropouche virus infection on the intracellular trafficking of amyloid precursor protein (APP) in mouse neurons.

• Grant number: 24/16105-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2024
• End date: September 30, 2025
• Field of knowledge: Biological Sciences - Microbiology
• Principal Investigator: Luis Lamberti Pinto da Silva
• Grantee: Maria Laura de Oliveira Costa
• 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 arbovirus of the Peribunyaviridae family and the Orthobunyavirus genus. Since its identification in the 1960s, it is estimated that at least half a million cases of OROV infection have occurred in Brazil. OROV is the causative agent of Oropouche fever, a febrile disease with symptoms similar to those of other tropical arboviruses and with the potential to progress to meningitis and encephalitis. However, the effects of OROV infection on the CNS in the medium and long term are completely unknown. In this sense, the project in question aims to investigate changes in neuronal proteostasis resulting from OROV infection, taking as reference the processing of the amyloid precursor protein, APP, and the associated production of beta-amyloid. Specifically, we will monitor changes in the trafficking, processing, clearance and secretion of neurotoxic fragments of APP. We will use neural cell culture from newborn mice associated with a set of techniques already standardized in the laboratory to study APP. The results may determine the contribution of OROV neuroinfection in the development of neurodegenerative disorders, a relevant question that is still open.