Molecular mechanisms of Oropouche Virus assembly

• Grant number: 19/02418-9
• Support type: Regular Research Grants
• Duration: April 01, 2019 - March 31, 2022
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Cooperation agreement: BBSRC, UKRI
• Principal researcher: Luis Lamberti Pinto da Silva
• Grantee: Luis Lamberti Pinto da Silva
• Principal researcher abroad: Colin Crump
• Institution abroad: University of Cambridge, England
• 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 one of the most common arboviruses that infects humans in South America. A conservative estimate is that half million people have been infected by OROV in Brazil since the virus was first identified in 1955, although this is likely to be an underestimate due to a resemblance of Oropouche fever with the symptoms of other arbovirus infections including Dengue, Zika and Chikungunya. Importantly, OROV has epidemic potential as several outbreaks have occurred in South America in the last 60 years. Understanding the molecular mechanisms underlying OROV replication in mammalian cells will be crucial for the development of future anti-OROV drugs, which are currently unavailable. OROV belongs to the Peribunyaviridae family, one of the largest families of RNA viruses. Until recently, the host cell machinery involved in Peribunyavirus assembly was unknown. Recently the da Silva group (São Paulo University) provided evidence that the cellular Endosomal Sorting Complex Required for Transport (ESCRT) machinery is recruited to OROV assembly sites associated with the Golgi complex (Barbosa et al., 2018). However, several important questions remain. In this project we will characterize the molecular mechanisms by which OROV recruits ESCRT components to Golgi membranes to facilitate virus production. (AU)