Respiratory syncytial virus co-opts host mitochondrial function to favour infectious virus production
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...
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doaj-c0881d4026df4c5a830306c47e5b44882021-05-05T17:43:35ZengeLife Sciences Publications LtdeLife2050-084X2019-06-01810.7554/eLife.42448Respiratory syncytial virus co-opts host mitochondrial function to favour infectious virus productionMengJie Hu0https://orcid.org/0000-0002-7362-1452Keith E Schulze1Reena Ghildyal2Darren C Henstridge3Jacek L Kolanowski4Elizabeth J New5Yuning Hong6Alan C Hsu7https://orcid.org/0000-0002-6640-0846Philip M Hansbro8Peter AB Wark9Marie A Bogoyevitch10https://orcid.org/0000-0001-9745-3716David A Jans11https://orcid.org/0000-0001-5115-4745Department of Biochemistry and Molecular Biology, University of Melbourne, Melbourne, Australia; Department of Biochemistry and Molecular Biology, Monash University, Melbourne, AustraliaMonash Micro Imaging, Monash University, Melbourne, AustraliaCentre for Research in Therapeutic Solutions, Faculty of Science and Technology, University of Canberra, Canberra, AustraliaBaker Heart and Diabetes Institute, Melbourne, AustraliaSchool of Chemistry, The University of Sydney, Sydney, AustraliaSchool of Chemistry, The University of Sydney, Sydney, AustraliaDepartment of Chemistry and Physics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, AustraliaPriority Research Centre for Healthy Lungs, Hunter Medical Research Institute (HMRI) and School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, AustraliaPriority Research Centre for Healthy Lungs, Hunter Medical Research Institute (HMRI) and School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, AustraliaPriority Research Centre for Healthy Lungs, Hunter Medical Research Institute (HMRI) and School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, AustraliaDepartment of Biochemistry and Molecular Biology, University of Melbourne, Melbourne, AustraliaDepartment of Biochemistry and Molecular Biology, Monash University, Melbourne, AustraliaAlthough 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.https://elifesciences.org/articles/42448respiratory syncytial virusinfectionmitochondriareactive oxygen species |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
MengJie Hu Keith E Schulze Reena Ghildyal Darren C Henstridge Jacek L Kolanowski Elizabeth J New Yuning Hong Alan C Hsu Philip M Hansbro Peter AB Wark Marie A Bogoyevitch David A Jans |
spellingShingle |
MengJie Hu Keith E Schulze Reena Ghildyal Darren C Henstridge Jacek L Kolanowski Elizabeth J New Yuning Hong Alan C Hsu Philip M Hansbro Peter AB Wark Marie A Bogoyevitch David A Jans Respiratory syncytial virus co-opts host mitochondrial function to favour infectious virus production eLife respiratory syncytial virus infection mitochondria reactive oxygen species |
author_facet |
MengJie Hu Keith E Schulze Reena Ghildyal Darren C Henstridge Jacek L Kolanowski Elizabeth J New Yuning Hong Alan C Hsu Philip M Hansbro Peter AB Wark Marie A Bogoyevitch David A Jans |
author_sort |
MengJie Hu |
title |
Respiratory syncytial virus co-opts host mitochondrial function to favour infectious virus production |
title_short |
Respiratory syncytial virus co-opts host mitochondrial function to favour infectious virus production |
title_full |
Respiratory syncytial virus co-opts host mitochondrial function to favour infectious virus production |
title_fullStr |
Respiratory syncytial virus co-opts host mitochondrial function to favour infectious virus production |
title_full_unstemmed |
Respiratory syncytial virus co-opts host mitochondrial function to favour infectious virus production |
title_sort |
respiratory syncytial virus co-opts host mitochondrial function to favour infectious virus production |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2019-06-01 |
description |
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. |
topic |
respiratory syncytial virus infection mitochondria reactive oxygen species |
url |
https://elifesciences.org/articles/42448 |
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