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.
journal_name
Elifejournal_title
eLifeauthors
Hu M,Schulze KE,Ghildyal R,Henstridge DC,Kolanowski JL,New EJ,Hong Y,Hsu AC,Hansbro PM,Wark PA,Bogoyevitch MA,Jans DAdoi
10.7554/eLife.42448subject
Has Abstractpub_date
2019-06-27 00:00:00issn
2050-084Xpii
42448journal_volume
8pub_type
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