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.

Scientific Reports
|February 29, 2020
PubMed

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.