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

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.

• Authors: 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
• Journal: eLife (Elife) Vol. 8 (06 27 2019) ISSN: 2050-084X [Electronic] England
• PMID: 31246170 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019, Hu et al.

Chemical References

• Dyneins

Topics

• A549 Cells
• Animals
• Disease Models, Animal
• Dyneins (metabolism)
• Host-Pathogen Interactions
• Humans
• Lung (pathology, virology)
• Mice
• Microtubules (metabolism)
• Mitochondria (pathology)
• Respiratory Syncytial Virus Infections (pathology)
• Respiratory Syncytial Viruses (growth & development)
• Virus Replication