Study on the role of the host cell protein ATG9 in Oropouche virus replication.

• Grant number: 24/22882-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: March 01, 2025
• End date: February 28, 2026
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Luis Lamberti Pinto da Silva
• Grantee: Kimberlly Medeiros de Azevedo
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The Oropouche virus (OROV) is a member of the Peribunyaviridae family within the order Bunyavirales and is responsible for causing Oropouche fever, a disease with significant impact in several countries in Central and South America. In the first half of 2024, there was a marked increase in the number of Oropouche fever cases in Brazil, with autochthonous reports in almost all states, including several where OROV infection had never been reported before. Despite its epidemiological relevance, limited knowledge of the mechanisms of viral replication, particle assembly, and evasion of the host antiviral response hinders the development of therapies to combat the disease. Studies suggest that viruses from other families within the order Bunyavirales, such as those from the Hantaviridae family, utilize the autophagic machinery for the production of viral particles. The protein ATG9 plays a central role in the autophagy process, being essential for the formation of autophagosomes. Preliminary, unpublished results obtained by our research group indicate that the deficiency of ATG9 leads to a reduction in the production of OROV particles. Furthermore, the AP-4 complex regulates the intracellular transport of several transmembrane proteins, including ATG9, and its deficiency disrupts the subcellular distribution of this protein. In this context, the overarching goal of the present study is to investigate the relationship between the function of ATG9 and the AP-4 complex in the replication of OROV, aiming to deepen our understanding of the mechanisms underlying OROV replication in human cells.