Impact of respiratory syncytial virus on host cell mitochondria

MJ Hu1, HM Li2, L Caly2, DA Stroud2, DC Henstridge3, MT Ryan2, MA Bogoyevitch1 and DA Jans2

  1. Department of Biochemistry and Molecular Biology, Cell Signaling Research Laboratories and Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, VIC 3010, Australia
  2. Department of Biochemistry and Molecular Biology, Monash University, Melbourne, VIC 3800, Australia
  3. Cellular and Molecular Metabolism Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, VIC 3004, Australia

The World Health Organization estimates that Respiratory syncytial virus (RSV) causes 64 million infections and 160,000 deaths annually worldwide, making it the chief cause of viral pneumonia in infants, with more deaths each year than influenza. Although the clinical manifestations of RSV infection are known, the physiopathological mechanisms involved in disease are not understood. Recent proteomic studies in model systems indicate an impact of RSV on a number of nuclear-encoded mitochondrial proteins, implying a potential effect of RSV on mitochondrial function. Here we evaluate for the first time the effect of RSV infection on mitochondrial organization and function in A549 human alveolar basal epithelial cells. We additionally document RSV-induced changes in mitochondrial membrane potential, expression of oxidative phosphorylation complexes and metabolic functions over the first 24 hours of infection, and across different multiplicities of infection (MOIs). Mechanistic insights have been provided through use of different mitochondrial knock-out cell lines, probing the contributions of host cell mitochondrial health in RSV infectivity and viral production. Our results highlight the importance of host cell mitochondria in RSV pathogenesis thus paving the way for new therapeutic interventions and the development of anti-viral strategies.