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An Improved and High Throughput Respiratory Syncytial Virus RSV Micro-neutralization Assay
Published on: January 26, 2019
Increased Lung Catalase Activity Confers Protection Against Experimental RSV Infection
Maria Ansar1, Teodora Ivanciuc2, Roberto P Garofalo1,2,3
1University of Texas Medical Branch, Department of Microbiology and Immunology Galveston, Galveston, TX, 77555, USA.
Abstract:
Respiratory syncytial virus (RSV) infection in mouse and human lung is associated with oxidative injury and pathogenic inflammation. RSV impairs antioxidant responses by increasing the degradation of transcription factor NRF2, which controls the expression of several antioxidant enzyme (AOE) genes, including catalase. Since catalase is a key enzyme for the dismutation of virus-mediated generation of hydrogen peroxide (H2O2) we developed a model of intranasal supplementation of polyethylene glycol-conjugated catalase (PG-CAT) for RSV-infected mice. The results of our study show that PG-CAT supplementation was able to increase specific enzymatic activity along with reduction in H2O2 in the airways and had a significant protective effect against RSV-induced clinical disease and airway pathology. PG-CAT treated mice showed amelioration in airway obstruction, reduction in neutrophil elastase and inflammation. Improved airway hyperresponsiveness was also observed in mice that received PG-CAT as a treatment post-viral inoculation. In addition, PG-CAT greatly reduced the concentration of inflammatory cytokines and chemokines, including IL-1, TNF-α, IL-9, CXCL1, CCL2, and CCL5 in the bronchoalveolar lavage fluid of RSV-infected mice, without increasing viral replication in the lung. In conclusion, catalase supplementation may represent a novel pharmacologic approach to be explored in human for prevention or treatment of respiratory infections caused by RSV.
Insights
Nrf2 antioxidant responses are impaired by respiratory syncytial virus (RSV). Supplementing with polyethylene glycol-conjugated catalase (PG-CAT) reduced oxidative stress and inflammation, offering protection against RSV-induced lung disease.
Area of Science:
- Respiratory viral infections
- Oxidative stress and inflammation
- Antioxidant enzyme therapy
Background:
- Respiratory syncytial virus (RSV) infection causes oxidative injury and inflammation in the lungs.
- RSV impairs antioxidant responses by degrading the transcription factor NRF2, reducing antioxidant enzyme expression.
- Catalase is crucial for neutralizing hydrogen peroxide (H₂O₂) generated during viral infections.
Purpose of the Study:
- To investigate the therapeutic potential of intranasal catalase supplementation in a mouse model of RSV infection.
- To evaluate the effects of polyethylene glycol-conjugated catalase (PG-CAT) on oxidative stress, inflammation, and disease severity in RSV-infected mice.
Main Methods:
- Development of an intranasal delivery model for PG-CAT in RSV-infected mice.
- Measurement of enzymatic activity, H₂O₂ levels, airway obstruction, and inflammation markers (neutrophil elastase, cytokines, chemokines).
- Assessment of airway hyperresponsiveness and viral replication in PG-CAT treated mice.
Main Results:
- PG-CAT treatment increased catalase activity and reduced H₂O₂ levels in the airways.
- Significant protection against RSV-induced clinical disease and airway pathology was observed.
- PG-CAT ameliorated airway obstruction, reduced inflammation, and improved airway hyperresponsiveness.
- Reduced levels of inflammatory cytokines and chemokines were found in bronchoalveolar lavage fluid without increased viral replication.
Conclusions:
- Catalase supplementation with PG-CAT demonstrates a protective effect against RSV-induced lung injury.
- PG-CAT effectively reduces oxidative stress and pathogenic inflammation associated with RSV infection.
- Catalase supplementation represents a potential novel therapeutic strategy for RSV prevention or treatment in humans.

