Viral-mediated Inhibition of Antioxidant Enzymes Contributes to the Pathogenesis of Severe Respiratory Syncytial Virus Bronchiolitis

• Published in: American journal of respiratory and critical care medicine Vol. 183; no. 11; pp. 1550 - 1560
• Main Authors: HOSAKOTE, Yashoda M, JANTZI, Paul D, ESHAM, Dana L, SPRATT, Heidi, KUROSKY, Alexander, CASOLA, Antonella, GAROFALO, Roberto P
• Format: Journal Article
• Language: English
• Published: New York, NY American Thoracic Society 01.06.2011
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Antioxidants; Antioxidants - metabolism; Auscultation; Biological and medical sciences; Biomarkers - metabolism; Blotting, Western; Bronchiolitis - etiology; Bronchiolitis - metabolism; Bronchoalveolar Lavage Fluid; Catalase - metabolism; Chronic obstructive pulmonary disease; Disease Models, Animal; Down-Regulation; Electrophoresis, Gel, Two-Dimensional; Emergency and intensive respiratory care; Enzymes; Female; G. Pulmonary Infections; Gene expression; Glutathione Peroxidase - metabolism; Glutathione Transferase - metabolism; Humans; Infections; Intensive care medicine; Lavage; Lungs; Medical sciences; Mice; Mice, Inbred BALB C; NF-E2-Related Factor 2 - metabolism; Oxidative Stress; Oxygen saturation; Pathogenesis; Respiratory syncytial virus; Respiratory Syncytial Virus Infections - complications; Respiratory Syncytial Virus Infections - metabolism; Respiratory Syncytial Viruses - metabolism; Severity of Illness Index; Sucrose; Superoxide Dismutase - metabolism; Transcription factors; Virus; Oxidative stress; Intensive care; Respiratory disease; Pathogenesis; Bronchus disease; airways; antioxidant enzymes; Antioxidant; respiratory syncytial virus; Resuscitation; Bronchiolitis
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.201010-1755OC

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.