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Study of Oropouche virus trafficking and its relationship with the autophagic pathway modulation during host cell infection

Grant number: 22/04533-2
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): September 01, 2022
Effective date (End): January 31, 2024
Field of knowledge:Biological Sciences - Microbiology
Principal Investigator:Luis Lamberti Pinto da Silva
Grantee:Kristel Irma Gutierrez Manchay
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

Oroupouche virus (OROV) has great epidemiological importance in Brazil and other South American countries such as Ecuador, Panama and Peru. OROV infection causes Oropouche fever, and in some cases may present manifestations of neurological disorders such as meningitis and encephalitis. In fact, studies using murine models and human brain slice cultures showed that OROV exhibits neurotropism, being able to replicate in neurons and microglia. OROV belongs to the Orthobunyavirus genus, which contains several arboviruses that cause disease in humans. Orthobunyaviruses are enveloped viruses with three segments of single-stranded RNA and negative polarity, encoding four structural proteins: surface glycoproteins (Gn and Gc), polymerase (L), and nucleocapsid protein (N); and two nonstructural proteins (NSm and NSs). Little is known about the cell biology of Orthobunyaviruses and their strategies to escape the host's antiviral response. Autophagy is an innate host mechanism that can destroy intracellular microorganisms such as viruses. However, viruses have developed various strategies to block autophagy and even subvert it for replication and release of progeny. Our research group found that OROV-infected H4 cells (human neuroglioma cells) produce viral factories that colocalize with autophagosome markers, indicating that autophagy is likely to be induced in the host cell. Therefore, this project aims to study the viral protein trafficking of OROV and its mechanism of viral replication in the host cell, through a possible relationship of these processes with the autophagic pathway.

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