The influence of Oropouche virus infection on the host cell autophagic pathway and its relationship with viral replication

Author(s)

Kristel Irma Gutierrez Manchay

• Document type: Master's Dissertation
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC)
• Defense date: 2024-04-08

Examining board members

Luis Lamberti Pinto da Silva; Gustavo Olszanski Acrani; Clarissa Rosa de Almeida Damaso

• Advisor: Luis Lamberti Pinto da Silva; Sonia Aparecida Lopes Correa

Abstract

Members of the Orthobunyavirus genus are responsible for several diseases in humans, including Oropouche fever caused by Oropouche virus (OROV), which has significant epidemiological importance in Brazil and other Central and South American countries such as Ecuador, Colombia, Panama and Peru. OROV was identified as a neurotropic virus, emphasizing the relevance of studying the infectious process. Understanding the cellular biology of Orthobunyavirus and its strategies for evading the host\'s antiviral response is still limited. The present study provides evidence that OROV infection in human neuroglioma (H4 cells) and HeLa cell lines promotes an induction of complete autophagic flux, and that elements of the autophagic machinery are necessary for efficient OROV replication. Specifically, OROV infection induces the generation and consumption of LC3-II and p62 during the replication cycle, and depletion of ATG5 and ATG9 leads to reduced infectious viral particle release. However, treatment with bafilomycin, an inhibitor of degradative autophagy, in the final stage of the replication cycle, does not compromise viral replication or the consumption of LC3-II induced by infection. Therefore, we propose that a form of secretory autophagy may be induced during infection, which contributes to efficient viral release. Consistently, analysis of the ultracentrifugation fractions containing extracellular vesicles and viral particles of conditioned media from infected cells showed higher levels of autophagic and late endosomal proteins compared to uninfected cells. These results indicate that the autophagic pathway is subverted by OROV for efficient viral production and propagation. (AU)

• FAPESP's process: 22/04533-2 - Study of Oropouche virus trafficking and its relationship with the autophagic pathway modulation during host cell infection
• Grantee: Kristel Irma Gutierrez Manchay
• Support Opportunities: Scholarships in Brazil - Master