Characterization of host cell factors involved in the budding and egress of Oropouche virus

• Grant number: 15/06142-7
• Support Opportunities: Scholarships in Brazil - Master
• Start date: June 01, 2015
• End date: January 31, 2017
• Field of knowledge: Biological Sciences - Microbiology
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• 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

Abstract

The Oropouche virus (OROV) is an arbovirus within the Bunyaviridae family, Orthobunyavirus genus and Simbu sorogroup. The OROV is the etiological agent of the Oropouche fever, the second most prevalent disease within the arboviroses after dengue in Brazil. It is estimated that around half a milion people have been infected in the last 48 years in Brazil. Its occurrence was restricted to the Amazon area, however, due to the deforestation and global warming, the risk of redristibution of the insects increased as well as the dissemination of the virus to other parts of Brazil and South America. The Oropouche fever has an abrupt beginning, with symptoms similar to other tropical diseases, such as: fever, headache and muscular pain. As the infection is characterized by non specific symptoms, the real number of infected people by OROV is probably understimated. Despite the huge importance in public health, not much is known about the replicative cycle of OROV. Therefore, the present study has the aim to amplify the knowledge of molecular mechanisms involved in the assembly, budding and egress of the virus. It is believed that most of the bunyavirus are packed in the Golgi apparatus (GA), creating a viral factory, which then fuses with the plasma membrane releasing the viral particles. However, the packing in other compartiments of the endomembrane system has been related for some bunyavirus. In fact, a recent study by our group indicates that the assemby of OROV occurs a compartament distict from the GA. In this project, we propose to identify this compartiment and understand the mechanism by which the viral particles are released. Specifically, we will test wether the exit proteins from the TGN and the biogenesis of multivesicular bodies have a role in the replicative cycle of OROV. Moreover, we will analyse if the Rab proteins involved in the release of exosomes (Rab27a, Rab27b and Rab35), have a role in the OROV egress. The better understand of these events will reveal important insights, still unknown, of how the OROV bud in host cells and the pathway of its egress. Therefore, generating significant information for better comprehension of OROV pathogeneses' mechanisms, which can then contribute for new strategies aiming the inhibition of 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)

SABINO-SANTOS, JR., GILBERTO; MOTTA MAIA, FELIPE GONCALVES; MARTINS, RONALDO BRAGANCA; GAGLIARDI, TALITA BIANCA; DE SOUZA, WILLIAM MARCIEL; MUYLAERT, RENATA LARA; DE SOUZA LUNA, LUCIANO KLEBER; MELO, DANILO MACHADO; CARDOSO, RICARDO DE SOUZA; BARBOSA, NATALIA DA SILVA; et al. Natural infection of Neotropical bats with hantavirus in Brazil. SCIENTIFIC REPORTS, v. 8, JUN 13 2018. (12/03700-0, 12/04096-0, 16/02568-2, 12/24150-9, 15/05354-0, 13/06380-0, 11/19897-5, 11/06810-9, 14/02438-6, 11/22663-6, 15/06142-7)