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Rab27a GTPase and its effector Myosin Va are host factors required for efficient Oropouche virus cell egress
Juan O Concha1,2, Kristel Gutierrez1,2, Natalia Barbosa1,2,3
1Virus Research Center, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Plos Pathogens
|August 30, 2024
Summary
Oropouche virus (OROV) uses the host cell protein Rab27a to spread within the body. This discovery offers new pathways for treating Oropouche fever, an arbovirus illness.
Area of Science:
- Virology
- Cell Biology
- Molecular Biology
Background:
- Oropouche virus (OROV) causes debilitating Oropouche fever in South America.
- OROV is an arbovirus belonging to the Peribunyaviridae family of RNA viruses.
- Key aspects of Peribunyaviridae replication, particularly assembly and egress, remain poorly understood.
Purpose of the Study:
- To investigate the host cell mechanisms involved in Oropouche virus (OROV) assembly and release.
- To identify host factors mediating intracellular transport of OROV and viral egress.
Main Methods:
- Investigated the role of small GTPase Rab27a in OROV-infected cells.
- Examined interactions between Rab27a, OROV glycoproteins, and viral compartments.
- Assessed the impact of Rab27a depletion and inhibition of its downstream effectors (Myosin Va, actin polymerization) on viral release.
Main Results:
- Rab27a mediates the intracellular transport of OROV-induced compartments.
- Rab27a interacts with OROV glycoproteins and is crucial for viral egress.
- Inhibition of Rab27a, Myosin Va, or actin polymerization impairs OROV trafficking and release.
Conclusions:
- Oropouche virus (OROV) hijacks the host cell's Rab27a pathway for intracellular transport and release.
- Rab27a-mediated mechanisms are essential for OROV replication and spread.
- Targeting the Rab27a pathway presents a potential therapeutic strategy for Oropouche fever.
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