RSV infection in mice is associated with features of lung fibrosis by histochemistry, micro-CT imaging and large scale 3D-microscopy

<bold>Rationale:</bold> RSV severe lower respiratory tract infections in early life are linked to recurrent wheezing, asthma, persistently reduced lung function and to increased risk of premature adult death from respiratory diseases. <bold>Objective:</bold> The objective of this study was to capture long-term structural changes of the lung and collagen deposition in an experimental mouse model of RSV infection. <bold>Methods:</bold> Groups of BALB/c mice were infected with RSV or saline control. Micro-CT lung imaging of the lungs was performed weekly for one month, when lungs were harvested for visualization and quantification of collagen deposition by multiphoton microscopy (MPM) and second harmonic generation microscopy (SHGM), Masson’s trichrome staining, and hydroxyproline assay. <bold>Results:</bold> Lung collagen was significantly increased during the period of observation in RSV-infected mice compared with PBS control group. Quantification of RSV-induced lung alterations by micro-CT-based density histograms, percent of poorly aerated tissue, and lung total volume correlated with the histologic findings and with MPM/SHGM imaging aided by tissue optical clearing technique for quantification of lung collagen deposition. <bold>Conclusions:</bold> Experimental RSV infection is associated with features of airway remodeling in mice