Respiratory Syncytial Virus co-opts host mitochondrial function to favour infectious virus production
- University of Melbourne, Australia
- Monash University, Australia
- University of Canberra, Australia
- Baker Heart and Diabetes Institute, Australia
- University of Sydney, Australia
- La Trobe University, Australia
- University of Newcastle, Australia
Abstract
Although respiratory syncytial virus (RSV) is responsible for more human deaths each year than influenza, its pathogenic mechanisms are poorly understood. Here high-resolution quantitative imaging, bioenergetics measurements and mitochondrial membrane potential- and redox-sensitive dyes are used to define RSV's impact on host mitochondria for the first time, delineating RSV-induced microtubule/dynein-dependent mitochondrial perinuclear clustering, and translocation towards the microtubule-organizing centre. These changes are concomitant with impaired mitochondrial respiration, loss of mitochondrial membrane potential and increased production of mitochondrial reactive oxygen species (ROS). Strikingly, agents that target microtubule integrity the dynein motor protein, or inhibit mitochondrial ROS production strongly suppresses RSV virus production, including in a mouse model with concomitantly reduced virus-induced lung inflammation. The results establish RSV's unique ability to co-opt host cell mitochondria to facilitate viral infection, revealing the RSV-mitochondrial interface for the first time as a viable target for therapeutic intervention.
Data availability
Data are being uploaded to Dryad (DOI: https://doi.org/10.5061/dryad.2n3162c). Customised scripts for quantitative analyses of mitochondrial distribution and results are publicly available throughhttps://gitlab.erc.monash.edu.au/mmi/mito
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Data from: Respiratory Syncytial Virus co-opts host mitochondrial function to favour infectious virus productionDryad Digital Repository, doi:10.5061/dryad.j1fd7.
Article and author information
Author details
MengJie MengJie Hu
Marie A Bogoyevitch
Funding
National Health and Medical Research Council (APP1002486)
- David Andrew Jans
National Health and Medical Research Council (APP1043511)
- David Andrew Jans
National Health and Medical Research Council (APP1103050)
- David Andrew Jans
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in accordance with The ACT Animal Welfare Act (1992) and the Australian Code of Practice for the Care and use of Animals for Scientific Purposes. The study protocol was approved by the Committee for Ethics in Animal Experimentation of the University of Canberra (project reference number CEAE 14-15).
Human subjects: Primary human bronchial epithelial cells (pBECs) were obtained from 4 healthy individuals who had no history of smoking or lung disease, had normal lung function, and gave written, informed consent to participate and have their data published, in accordance with the procedures in accordance with the procedures approved by the University of Newcastle Human Ethics Committee (project reference no. H-163-1205), in keeping with the guidelines of the National Institutes of Health, American Academy of Allergy and Immunology.
Copyright
© 2019, Hu et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Respiratory Syncytial Virus co-opts host mitochondrial function to favour infectious virus production
eLife 8:e42448.
https://doi.org/10.7554/eLife.42448
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