Viral-mediated Inhibition of Antioxidant Enzymes Contributes to the Pathogenesis of Severe Respiratory Syncytial Virus Bronchiolitis
- 1 June 2011
- journal article
- Published by American Thoracic Society in American Journal of Respiratory and Critical Care Medicine
- Vol. 183 (11), 1550-1560
- https://doi.org/10.1164/rccm.201010-1755oc
Abstract
Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in children, for which no specific treatment or vaccine is currently available. We have previously shown that RSV induces reactive oxygen species in cultured cells and oxidative injury in the lungs of experimentally infected mice. The mechanism(s) of RSV-induced oxidative stress in vivo is not known. To measure changes of lung antioxidant enzymes expression/activity and activation of NF-E2-related factor 2 (Nrf2), a transcription factor that regulates detoxifying and antioxidant enzyme gene expression, in mice and in infants with naturally acquired RSV infection. Superoxide dismutase 1 (SOD 1), SOD 2, SOD 3, catalase, glutathione peroxidase, and glutathione S-transferase, as well as Nrf2 expression, were measured in murine bronchoalveolar lavage, cell extracts of conductive airways, and/or in human nasopharyngeal secretions by Western blot and two-dimensional gel electrophoresis. Antioxidant enzyme activity and markers of oxidative cell injury were measured in either murine bronchoalveolar lavage or nasopharyngeal secretions by colorimetric/immunoassays. RSV infection induced a significant decrease in the expression and/or activity of SOD, catalase, glutathione S-transferase, and glutathione peroxidase in murine lungs and in the airways of children with severe bronchiolitis. Markers of oxidative damage correlated with severity of clinical illness in RSV-infected infants. Nrf2 expression was also significantly reduced in the lungs of viral-infected mice. RSV infection induces significant down-regulation of the airway antioxidant system in vivo, likely resulting in lung oxidative damage. Modulation of oxidative stress may pave the way toward important advances in the therapeutic approach of RSV-induced acute lung disease.Keywords
This publication has 54 references indexed in Scilit:
- Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysisLancet, 2010
- Nrf2:INrf2 (Keap1) signaling in oxidative stressFree Radical Biology & Medicine, 2009
- Respiratory Syncytial Virus Induces Oxidative Stress by Modulating Antioxidant EnzymesAmerican Journal of Respiratory Cell and Molecular Biology, 2009
- Antiviral Activity of Nrf2 in a Murine Model of Respiratory Syncytial Virus DiseaseAmerican Journal of Respiratory and Critical Care Medicine, 2009
- Oxidants and the pathogenesis of lung diseasesJournal of Allergy and Clinical Immunology, 2008
- Identification of human metapneumovirus-induced gene networks in airway epithelial cells by microarray analysisVirology, 2008
- Antioxidant Treatment Ameliorates Respiratory Syncytial Virus–induced Disease and Lung InflammationAmerican Journal of Respiratory and Critical Care Medicine, 2006
- Human Metapneumovirus Induces a Profile of Lung Cytokines Distinct from That of Respiratory Syncytial VirusJournal of Virology, 2005
- Isolation of rodent airway epithelial cell proteins facilitates in vivo proteomics studies of lung toxicityAmerican Journal of Physiology-Lung Cellular and Molecular Physiology, 2004
- Reactive Oxygen Species Mediate Virus-induced STAT ActivationPublished by Elsevier BV ,2004