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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 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
Objective Field:	Clinical health not elsewhere classified
UTAS Author:	Henstridge, DC (Mr Darren Henstridge)
ID Code:	133539
Year Published:	2019
Web of Science® Times Cited:	14
Deposited By:	Health Sciences
Deposited On:	2019-07-01
Last Modified:	2019-08-05
Downloads:	18 View Download Statistics