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

• Grant number: 16/18356-4
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Effective date (Start): March 01, 2017
• Effective date (End): October 31, 2020
• Field of knowledge: Biological Sciences - Microbiology
• Principal Investigator: Luis Lamberti Pinto da Silva
• Grantee: Natalia da Silva Barbosa
• Host 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
• Associated scholarship(s): 19/02945-9 - Study of the molecular mechanisms involved in the oropouche virus assembly pathway, BE.EP.DD

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)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

BARBOSA, NATALIA S. S.; CONCHA, JUAN O. O.; DASILVA, LUIS L. P.; CRUMP, COLIN M. M.; GRAHAM, STEPHEN C. C.. Oropouche Virus Glycoprotein Topology and Cellular Requirements for Glycoprotein Secretion. Journal of Virology, v. 97, n. 1, p. 16-pg., 2022-12-08. (19/02418-9, 19/02945-9, 16/18356-4)