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Study of the molecular mechanisms involved in the oropouche virus assembly pathway

Grant number: 19/02945-9
Support Opportunities:Scholarships abroad - Research Internship - Doctorate (Direct)
Start date: May 01, 2019
End date: March 31, 2020
Field of knowledge:Biological Sciences - Microbiology
Principal Investigator:Luis Lamberti Pinto da Silva
Grantee:Natalia da Silva Barbosa
Supervisor: Colin Crump
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Institution abroad: University of Cambridge, England  
Associated to the scholarship:16/18356-4 - Study of host cellular factors involved in assembly and budding of Orthobunyavirus using Oropouche virus as a model, BP.DD

Abstract

Oropouche virus (OROV) is an arbovirus that belongs to the Orthobunyavirus genus, and is the etiological agent of Oropouche fever, a febrile illness common in South America. It has been estimated that approximately half a million people have been infected by OROV in Brazil during the last 50 years. Despite its importance in public health, the replicative cycle of this arbovirus is poorly understood. It is becoming clearer that the main assembly site of Orthobunyaviruses is the Golgi complex. Indeed, we observed in our studies that the Golgi complex morphology is altered during OROV infection. As viral replication progresses, Golgi cisternae become enlarged and physically separated from the Golgi complex. These structures are termed "viral vesicles". Moreover, we also observed that these vesicles presented a multivesicular body appearance. Thus, we investigated the involvement of Endosomal Sorting Complex Required for Transport (ESCRT) and demonstrated that this complex is necessary for OROV production. One of the most interesting findings of our study was that ESCRT components appeared to colocalise with Golgi markers and OROV proteins during viral infection. However, we were unable to provide definitive proof that ESCRTs are recruited to the Golgi complex during OROV assembly. Therefore, we propose to study the association of ESCRT components with Golgi membranes during OROV infection in further detail. Furthermore, we also propose to investigate whether there is a physical interaction between OROV structural proteins and ESCRT components. The work proposed here would very nicely complement my graduate studies funded by FAPESP (2016/18356-4) and will also contribute to a better understanding of how Orthobunyaviruses hijack host components to achieve efficient virus production. (AU)

News published in Agência FAPESP Newsletter about the scholarship:
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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., . (19/02418-9, 19/02945-9, 16/18356-4)