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Published (Version of record)CC BY V4.0, Open Access
Published (Version of record)CC BY V4.0, Open
Journal article
Respiratory syncytial virus co-opts host mitochondrial function to favour infectious virus production
ELife, Vol.8, e42448
27/06/2019
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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.
Details
- Title
- Respiratory syncytial virus co-opts host mitochondrial function to favour infectious virus production
- Creators
- Meng Jie Hu - University of MelbourneKeith E Schulze - Monash UniversityReena Ghildyal - University of CanberraDarren C Henstridge - Baker Heart and Diabetes InstituteJacek L Kolanowski - University of SydneyElizabeth J New - University of SydneyYuning Hong - La Trobe UniversityAlan C Hsu - University of Newcastle AustraliaPhilip M Hansbro - University of Newcastle AustraliaPeter A. B Wark - University of Newcastle AustraliaMarie A Bogoyevitch - University of MelbourneDavid A Jans - Monash University
- Publication Details
- ELife, Vol.8, e42448
- Publisher
- eLife Sciences Publications
- Identifiers
- 991013036785302368
- Academic Unit
- National Centre for Naturopathic Medicine
- Language
- English
- Resource Type
- Journal article