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Respiratory syncytial virus co-opts host mitochondrial function to favour infectious virus production
Citation
Hu, M and Schulze, KE and Ghildyal, R and Henstridge, DC and Kolanowski, JL and New, EJ and Hong, Y and Hsu, AC and Hansbro, PM and Wark, PAB and Bogoyevitch, MA and Jans, DA, Respiratory syncytial virus co-opts host mitochondrial function to favour infectious virus production, eLife, 8 pp. e42448. ISSN 2050-084X (2019) [Refereed Article]
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Copyright Statement
Copyright 2019 Hu et al. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/
DOI: doi:10.7554/eLife.42448.001
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.
Item Details
Item Type: | Refereed Article |
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Keywords: | virus, human, infection, infectious disease, microbiology, mitochondria, reactive oxygen species, respiratory syncytial virus |
Research Division: | Biological Sciences |
Research Group: | Biochemistry and cell biology |
Research Field: | Cell metabolism |
Objective Division: | Health |
Objective Group: | Clinical health |
Objective Field: | Clinical health not elsewhere classified |
UTAS Author: | Henstridge, DC (Dr Darren Henstridge) |
ID Code: | 133539 |
Year Published: | 2019 |
Web of Science® Times Cited: | 22 |
Deposited By: | Health Sciences |
Deposited On: | 2019-07-01 |
Last Modified: | 2022-08-24 |
Downloads: | 23 View Download Statistics |
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