Study of the possible function of the autophagic machinery in the assembly and externalization of the Oropouche virus.

• Grant number: 24/09772-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: October 01, 2024
• End date: March 31, 2028
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Luis Lamberti Pinto da Silva
• Grantee: Kristel Irma Gutierrez Manchay
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Members of the Peribunyaviridae family of the genus Orthobunyavirus are causative agents of several diseases in humans, including Oropouche fever caused by the Oropouche virus (OROV), which has significant epidemiological importance in Brazil and other Central and South American countries, such as Colombia. , Bolivia, Panama and Peru. OROV was identified as a neurotropic virus, emphasizing the relevance of studying the infectious process. Understanding the cell biology of Orthobunyaviruses, especially the mechanisms of assembly and egress of viral particles and their strategies for evading the host's antiviral response, is still limited. Recent studies in other families of the order Bunyavirales (family Hantaviridae and Phenuiviridae) have demonstrated that the induction of the host cell's autophagic pathway can favor viral replication. Although the autophagic pathway can act as an antiviral pathway, many RNA viruses have evolved to antagonize this antiviral cellular response and induce the accumulation of autophagic membranes as scaffolds for viral replication complexes and/or to facilitate the release of viral particles. Our preliminary results show that human cells infected with OROV present induction of autophagic flux, and that elements of the autophagic machinery are necessary for their efficient replication. Furthermore, it was observed that cells infected with OROV secrete proteins related to the secretory autophagy pathway. These results could indicate that the autophagic pathway is subverted by OROV for efficient viral production and propagation. Based on this hypothesis, the objective of the present work is to analyze the relationship between autophagy and the replication of the Oropouche virus, focusing on its possible function as a facilitator of viral assembly and externalization processes.