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

Although respiratory syncytial virus (RSV) is responsible for more human deaths eachyear than influenza, its pathogenic mechanisms are poorly understood. Here high-resolutionquantitative imaging, bioenergetics measurements and mitochondrial membrane potential- andredox-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, andtranslocation towards the microtubule-organizing centre. These changes are concomitant withimpaired mitochondrial respiration, loss of mitochondrial membrane potential and increasedproduction of mitochondrial reactive oxygen species (ROS). Strikingly, agents that targetmicrotubule integrity the dynein motor protein, or inhibit mitochondrial ROS production stronglysuppresses 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 cellmitochondria to facilitate viral infection, revealing the RSV-mitochondrial interface for the first timeas a viable target for therapeutic intervention.