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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 RSVís 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 RSVís 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
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 (Organs, Diseases and Abnormal Conditions)
Objective Field:Infectious Diseases
UTAS Author:Henstridge, DC (Mr Darren Henstridge)
ID Code:133539
Year Published:2019
Web of Science® Times Cited:1
Deposited By:Health Sciences
Deposited On:2019-07-01
Last Modified:2019-08-05
Downloads:3 View Download Statistics

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