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

• Grant number: 19/02945-9
• Support type: Scholarships abroad - Research Internship - Doctorate (Direct)
• Effective date (Start): May 01, 2019
• Effective date (End): March 31, 2020
• Field of knowledge: Biological Sciences - Microbiology
• Principal researcher: Luis Lamberti Pinto da Silva
• Grantee: Natalia da Silva Barbosa
• Supervisor abroad: Colin Crump
• Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Research place: 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)