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

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Hu, M, Schulze, KE, Ghildyal, R, Henstridge, DC ORCID: 0000-0003-4988-767X, Kolanowski, JL, New, EJ, Hong, Y, Hsu, AC, Hansbro, PM, Wark, PAB, Bogoyevitch, MA and Jans, DA 2019 , 'Respiratory syncytial virus co-opts host mitochondrial function to favour infectious virus production' , eLife, vol. 8 , e42448 , doi: 10.7554/eLife.42448.001.

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Abstract

Although respiratory syncytial virus (RSV) is responsible for more human deaths eachyear than influenza, its pathogenic mechanisms are poorly understood. Here high-resolutionquantitative imaging, bioenergetics measurements and mitochondrial membrane potential- andredox-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, andtranslocation towards the microtubule-organizing centre. These changes are concomitant withimpaired mitochondrial respiration, loss of mitochondrial membrane potential and increasedproduction of mitochondrial reactive oxygen species (ROS). Strikingly, agents that targetmicrotubule integrity the dynein motor protein, or inhibit mitochondrial ROS production stronglysuppresses 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 cellmitochondria to facilitate viral infection, revealing the RSV-mitochondrial interface for the first timeas a viable target for therapeutic intervention.

Item Type: Article
Authors/Creators: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
Keywords: virus, human, infection, infectious disease, microbiology, mitochondria, reactive oxygen species, respiratory syncytial virus
Journal or Publication Title: eLife
Publisher: eLife Sciences Publications Ltd.
ISSN: 2050-084X
DOI / ID Number: 10.7554/eLife.42448.001
Copyright Information:

Copyright 2019 Hu et al. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

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