Respiratory syncytial virus induces oxidative stress by modulating antioxidant enzymes

Am J Respir Cell Mol Biol. 2009 Sep;41(3):348-57. doi: 10.1165/rcmb.2008-0330OC. Epub 2009 Jan 16.


Oxidative stress plays an important role in the pathogenesis of lung inflammation. Respiratory syncytial virus (RSV) infection induces reactive oxygen species (ROS) production in vitro and oxidative injury in lungs in vivo; however, the mechanism of RSV-induced cellular oxidative stress has not been investigated. Therefore, we determined whether RSV infection of airway epithelial cells modified the expression and/or activities of antioxidant enzymes (AOE). A549 cells, a human alveolar type II-like epithelial cell line, and small airway epithelial (SAE) cells, normal human cells derived from terminal bronchioli, were infected with RSV and harvested at various time points to measure F(2)-8 isoprostanes by enzyme-linked immunosorbent assay and total and reduced glutathione (GSH and GSSG) by colorimetric assay. Superoxide dismutase (SOD) 1, 2, and 3, catalase, glutathione peroxidase (GPx), and glutathione S-transferase (GST) expression was determined by quantitative real-time PCR and Western blot, and their activity was measured by colorimetric assays. RSV infection induced a significant increase of lipid peroxidation products as well as a significant decrease in the GSH/GSSG ratio. There was a significant decrease in SOD 1, SOD 3, catalase, and GST expression with a concomitant increase of SOD 2 in RSV-infected cells, compared with uninfected cells. Total SOD activity was increased, but catalase, GPx, and GST activities were decreased, after RSV infection. Our findings suggest that RSV-induced cellular oxidative damage is the result of an imbalance between ROS production and antioxidant cellular defenses. Modulation of oxidative stress represents a potential novel pharmacologic approach to ameliorate RSV-induced acute lung inflammation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / metabolism*
  • Catalase / genetics
  • Catalase / metabolism
  • Cell Line
  • Chemokine CCL5 / metabolism
  • Child
  • Glutathione Peroxidase / genetics
  • Glutathione Peroxidase / metabolism
  • Glutathione Transferase / genetics
  • Glutathione Transferase / metabolism
  • Humans
  • Infant
  • Interleukin-8 / metabolism
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • NF-E2-Related Factor 2 / metabolism
  • Oxidative Stress*
  • Reactive Oxygen Species / metabolism
  • Respiratory Mucosa / cytology
  • Respiratory Syncytial Viruses / metabolism*
  • Respiratory Syncytial Viruses / pathogenicity
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism


  • Antioxidants
  • Chemokine CCL5
  • Interleukin-8
  • Isoenzymes
  • NF-E2-Related Factor 2
  • Reactive Oxygen Species
  • Catalase
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Glutathione Transferase