Rab27a GTPase and its effector Myosin Va are host factors required for efficient Oropouche virus cell egress

Juan O Concha; Kristel Gutierrez; Natalia Barbosa; Roger L Rodrigues; Andreia N de Carvalho; Lucas A Tavares; Jared S Rudd; Cristina S Costa; Barbara Y G Andrade; Enilza M Espreafico; Colin M Crump; Luis L P daSilva

doi:10.1371/journal.ppat.1012504

Rab27a GTPase and its effector Myosin Va are host factors required for efficient Oropouche virus cell egress

PLoS Pathog. 2024 Aug 30;20(8):e1012504. doi: 10.1371/journal.ppat.1012504. eCollection 2024 Aug.

Authors

Juan O Concha^{1

2}, Kristel Gutierrez^{1

2}, Natalia Barbosa^{1

2

3}, Roger L Rodrigues^{1

2}, Andreia N de Carvalho^{1

2}, Lucas A Tavares^{1

2}, Jared S Rudd^{1

2}, Cristina S Costa^{1

2}, Barbara Y G Andrade², Enilza M Espreafico², Colin M Crump³, Luis L P daSilva^{1

2}

Affiliations

¹ Virus Research Center, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
² Department of Cell and Molecular Biology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
³ Department of Pathology, University of Cambridge, Cambridge, United Kingdom.

Abstract

Oropouche fever, a debilitating illness common in South America, is caused by Oropouche virus (OROV), an arbovirus. OROV belongs to the Peribunyaviridae family, a large group of RNA viruses. Little is known about the biology of Peribunyaviridae in host cells, especially assembly and egress processes. Our research reveals that the small GTPase Rab27a mediates intracellular transport of OROV induced compartments and viral release from infected cells. We show that Rab27a interacts with OROV glycoproteins and colocalizes with OROV during late phases of the infection cycle. Moreover, Rab27a activity is required for OROV trafficking to the cell periphery and efficient release of infectious particles. Consistently, depleting Rab27a's downstream effector, Myosin Va, or inhibiting actin polymerization also hinders OROV compartments targeting to the cell periphery and infectious viral particle egress. These data indicate that OROV hijacks Rab27a activity for intracellular transport and cell externalization. Understanding these crucial mechanisms of OROV's replication cycle may offer potential targets for therapeutic interventions and aid in controlling the spread of Oropouche fever.

Copyright: © 2024 Concha et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

MeSH terms

Animals
Bunyaviridae Infections / metabolism
Bunyaviridae Infections / virology
Host-Pathogen Interactions
Humans
Myosin Heavy Chains* / metabolism
Myosin Type V* / genetics
Myosin Type V* / metabolism
Orthobunyavirus / metabolism
Orthobunyavirus / physiology
Virus Release* / physiology
Virus Replication / physiology
rab27 GTP-Binding Proteins* / metabolism

Substances

rab27 GTP-Binding Proteins
Myosin Type V
MYO5A protein, human
RAB27A protein, human
Myosin Heavy Chains

Grants and funding

This work was funded by the São Paulo Research Foundation (FAPESP) and Biotechnology and Biological Sciences Research Council pump priming awards 2019/02418-9 and BB/S018670/1 to LLPdS and CMC, respectively. LLPdS is thankful to the Academy of Medical Sciences for a Newton Advanced Fellowship. The work was also funded by grants from FAPESP (2018/00297-7 and 2019/26119-0) and Fundação de Apoio ao Ensino, Pesquisa e Assistência do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (FAEPA) to LLPdS. Finally, this work was also supported by FAPESP studentships to JOC, KG, NSB, and CSC (respectively, 2020/11900-6, 2022/04533-2, 2016/18356-4, and 2019/27725-1), Postdoctoral fellowships by FAPESP to LAT and JSR (2021/01182-1 and 2023/02880-0), and traveling fellowship to NSB (2019/02945-9). LLPdS is recipient of a long-standing investigator scholarship from CNPq. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.