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Study of Oropouche virus assembly mechanism in neurons and its effects on the cellular proteostasis

Grant number: 19/08461-3
Support type:Scholarships in Brazil - Master
Effective date (Start): July 01, 2019
Effective date (End): October 31, 2021
Field of knowledge:Biological Sciences - Morphology - Cytology and Cell Biology
Principal researcher:Luis Lamberti Pinto da Silva
Grantee:Luan dos Santos de Oliveira
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:14/02438-6 - Studies with Bunyaviridae that produce human disease, AP.TEM

Abstract

Oropouche Virus (OROV) is an enveloped arbovirus of the Peribunyaviridae family and the Orthobunyavirus genus. More than half million cases of OROV infection were estimated to occur in Brazil since the 60's, when the virus was discovered. OROV is responsible for the Oropouche fever, a febrile disease with symptoms similar to diseases caused by other frequent tropical arboviruses, with the potential to evolve to encephalitis and meningitis. Despite its predominance in the country and threat to the public health, it is believed that OROV is still an underestimated virus, mainly because of the lack of an accurate diagnosis and reduced number of studies about its biology. One of the main factors that elevate the degree of danger of OROV infection is its neurotropism, with studies demonstrating that the virus can reach the central nervous system. Furthermore, it was recently discovered that OROV uses the ESCRT machinery from host cells during its replicative cycle. The ESCRT machinery is important in the regulation of endocytic pathways and in the last years studies pointed that its components are related with beta-amyloid generation. The beta-amyloid peptides are generated through the processing of the amyloid precursor protein in neurons and can form aggregates with each other. The abnormal increase in beta-amyloid generation and eventual formation of beta-amyloid plaques in the brain is considered one of the pathologic hallmarks in Alzheimer's disease. Currently, little is known about the details of the replicative cycle of OROV in neurons and how OROV infection can alter the proteostasis of host cells. Therefore, the objective of this project is to elucidate the replicative cycle of OROV in neurons and to investigate whether infection leads to alterations in normal protein trafficking in these cells, thus providing more details about the pathogenesis of the virus in the nervous system.

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