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Elife. 2019 Jun 27;8. pii: e42448. doi: 10.7554/eLife.42448.

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

Author information

1
Department of Biochemistry and Molecular Biology, University of Melbourne, Melbourne, Australia.
2
Department of Biochemistry and Molecular Biology, Monash University, Melbourne, Australia.
3
Monash Micro Imaging, Monash University, Melbourne, Australia.
4
Centre for Research in Therapeutic Solutions, Faculty of Science and Technology, University of Canberra, Canberra, Australia.
5
Baker Heart and Diabetes Institute, Melbourne, Australia.
6
School of Chemistry, The University of Sydney, Sydney, Australia.
7
Department of Chemistry and Physics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Australia.
8
Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute (HMRI) and School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, Australia.
#
Contributed equally

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.

KEYWORDS:

human; infection; infectious disease; microbiology; mitochondria; reactive oxygen species; respiratory syncytial virus

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