Micro-CT Features of Lung Consolidation, Collagen Deposition and Inflammation in Experimental RSV Infection Are Aggravated in the Absence of Nrf2.
Teodora IvanciucIgor PatrikeevYue QuMassoud MotamediYava L Jones-HallAntonella CasolaRoberto P GarofaloPublished in: Viruses (2023)
Severe respiratory syncytial virus (RSV) infections in early life have been linked to the development of chronic airway disease. RSV triggers the production of reactive oxygen species (ROS), which contributes to inflammation and enhanced clinical disease. NF-E2-related factor 2 (Nrf2) is an important redox-responsive protein that helps to protect cells and whole organisms from oxidative stress and injury. The role of Nrf2 in the context of viral-mediated chronic lung injury is not known. Herein, we show that RSV experimental infection of adult Nrf2-deficient BALB/c mice ( Nrf2 -/- ; Nrf2 KO) is characterized by enhanced disease, increased inflammatory cell recruitment to the bronchoalveolar compartment and a more robust upregulation of innate and inflammatory genes and proteins, compared to wild-type Nrf2 +/+ competent mice (WT). These events that occur at very early time points lead to increased peak RSV replication in Nrf2 KO compared to WT mice (day 5). To evaluate longitudinal changes in the lung architecture, mice were scanned weekly via high-resolution micro-computed tomography (micro-CT) imaging up to 28 days after initial viral inoculation. Based on micro-CT qualitative 2D imaging and quantitative reconstructed histogram-based analysis of lung volume and density, we found that RSV-infected Nrf2 KO mice developed significantly greater and prolonged fibrosis compared to WT mice. The results of this study underscore the critical role of Nrf2-mediated protection from oxidative injury, not only in the acute pathogenesis of RSV infection but also in the long-term consequences of chronic airway injury.
Keyphrases
- oxidative stress
- respiratory syncytial virus
- induced apoptosis
- wild type
- high resolution
- computed tomography
- dna damage
- diabetic rats
- high fat diet induced
- ischemia reperfusion injury
- respiratory tract
- contrast enhanced
- magnetic resonance imaging
- image quality
- early life
- immune response
- dual energy
- sars cov
- drug induced
- type diabetes
- systematic review
- cell death
- mass spectrometry
- insulin resistance
- inflammatory response
- positron emission tomography
- cell proliferation
- bone marrow
- cross sectional
- adipose tissue
- single cell
- binding protein
- mesenchymal stem cells
- skeletal muscle
- magnetic resonance
- high speed
- acute respiratory distress syndrome
- metabolic syndrome
- amino acid