Respiratory Syncytial Virus co-opts host mitochondrial function to favour infectious virus production

Abstract
Data availability
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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

The following data sets were generated

1. Hu M
2. Schulze K
3. Ghildyal R
4. Henstridge D
5. Kolanowski J
6. New E
7. Hong Y
8. Hsu A
9. Hansbro P
10. Wark P
11. Bogoyevitch M
12. Jans D
(2019) Data from: Respiratory Syncytial Virus co-opts host mitochondrial function to favour infectious virus production
Dryad Digital Repository, doi:10.5061/dryad.j1fd7.

https://dx.doi.org/10.5061/dryad.2n3162

Article and author information

Author details

MengJie MengJie Hu

Department of Biochemistry and Molecular Biology, University of Melbourne, Melbourne, Australia

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-7362-1452
Keith E Schulze

Monash Micro Imaging, Monash University, Melbourne, Australia

Competing interests
The authors declare that no competing interests exist.
Reena Ghildyal

Centre for Research in Therapeutic Solutions, University of Canberra, Canberra, Australia

Competing interests
The authors declare that no competing interests exist.
Darren C Henstridge

Cellular and Molecular Metabolism Laboratory, Baker Heart and Diabetes Institute, Melbourne, Australia

Competing interests
The authors declare that no competing interests exist.
Jacek L Kolanowski

School of Chemistry, University of Sydney, Sydney, Australia

Competing interests
The authors declare that no competing interests exist.
Elizabeth J New

School of Chemistry, University of Sydney, Sydney, Australia

Competing interests
The authors declare that no competing interests exist.
Yuning Hong

Department of Chemistry and Physics, La Trobe University, Melbourne, Australia

Competing interests
The authors declare that no competing interests exist.
Alan C Hsu

Priority Research Centre for Healthy Lungs, University of Newcastle, Newcastle, Australia

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-6640-0846
Philip M Hansbro

Priority Research Centre for Healthy Lungs, University of Newcastle, Newcastle, Australia

Competing interests
The authors declare that no competing interests exist.
Peter AB Wark

Priority Research Centre for Healthy Lungs, University of Newcastle, Newcastle, Australia

Competing interests
The authors declare that no competing interests exist.
Marie A Bogoyevitch

Department of Biochemistry and Molecular Biology, University of Melbourne, Melbourne, Australia

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-9745-3716
David Andrew Jans

Department of Biochemistry and Molecular Biology, Monash University, Melbourne, Australia

For correspondence
David.Jans@monash.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-5115-4745

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

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.