Investigations into assembly, egress and virus-host interactions of Oropouche Virus

Tri-segmented bunyaviruses, which includes Rift valley fever virus and Oropouche virus (OROV), are responsible for a variety of human diseases ranging from self-limiting symptoms such as acute febrile illness, to lethal encephalitis and haemorrhagic fever. OROV is the first example of a virus shown to recruit endosomal sorting complex required for transport (ESCRT) components to virus assembly sites in the Golgi, through unclear mechanisms. During this project, I will develop virus-like particle assays to determine whether ESCRT recruitment is conserved across representative tri-segmented bunyavirus families. Once this has been established, I will investigate the molecular mechanisms that drive ESCRT recruitment to sites of bunyavirus assembly. I will do this by employing a range of proteomic approaches, that will utilise exogenously expressed bunyavirus envelope glycoproteins to identify potential interaction partners that are involved in ESCRT recruitment. Finally, I will conduct experiments using live OROV in collaborative research trips to Brazil, to understand how the virus changes the proteome of the cell during infection using a variety OROV mutants. These studies will elucidate a potentially novel mechanism of ESCRT recruitment during virus assembly and provide detailed understanding of bunyavirus-host interactions. Such new insights into bunyavirus infections may aid in development of antivirals.