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Study of host cellular factors involved in assembly and budding of Orthobunyavirus using Oropouche virus as a model

Grant number: 16/18356-4
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): March 01, 2017
Effective date (End): February 28, 2019
Field of knowledge:Biological Sciences - Microbiology
Principal Investigator:Luis Lamberti Pinto da Silva
Grantee:Natalia da Silva Barbosa
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

The Bunyaviridae family is one of the largest and most diverse RNA virus family. They have about 350 different isolates which represents a threat in public health and agricultural production. These viruses can be transmitted by aerosol particles or by invertebrate insects. Most of these pathogenic agents can cause hemorrhagic fever, fatal hepatitis, encephalitis or acute fever. Among the Orthobunyavirus genus there is the Oropouche virus (OROV) which is mostly encountered in South America. Little is known about the characteristics of assembly and budding pathway of Orthobunyavirus. Basically, all of the collected data nowadays are based on the Bunyamwera virus (BUNV). As for that, it is believed that most of the Bunyavirus, based on studies with BUNV, uses the Golgi complex as the main assembly site for its viral particles. However, there are conflicted data relating the assembly sites of Bunyavirus in the literature. Thus, the present work has the aim to amplify the knowledge about the molecular mechanisms involved in assembly, budding and externalization of Orthobunyavirus, using OROV as a model and comparing other species from this genus. Indeed, the data acquired during the Master's degree indicates that the assembly of OROV do not occurs directly in the Golgi complex. Our results also shows that the multivesicle bodies (MVBs) and the crucial role of the ESCRT machinery (Endosomal Sorting Complex Required for Transport) are important for the assembly and externalization of OROV, which has not been related to any Bunyavirus yet. In this project, we propose to establish the specific role of the ESCRT machinery and which exact components of this complex are involved in the OROV cycle. Additionally, we will analyse the possible role of the Rab proteins (Rab27a, Rab27b e Rab35), which are involved on the exosome release, with the externalization pathway of OROV. Posteriorly, we will use others Orthobunyaviruses, the Catú and Guamá viruses, to analyse if our findings relating to the assembly and budding pathways of OROV are conserved among this genus. The better understanding of these events, will revel important aspects, still unknown, involved in the assembly and externalization pathway of OROV in human cells. This way, presenting significant information for a better understanding of the assembly mechanisms of Bunyavirus, contributing to new strategies aiming to inhibit viral replication. (AU)

Articles published in Agência FAPESP about the scholarship:
Study shows how Oropouche virus replicates in human cells 
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