LSC 2014 abstract - Influenza infection may cause exacerbation of lung fibrosis through collagen deposition

Activated TGFβ promotes pro-apoptotic pathways in lung epithelial cells, which has been implicated in the pathogenesis of IPF. The Influenza-A virus infects epithelial cells leading to cell death and injury, and can also activate TGFβ. The rhinovirus causes common cold. Pulmonary fibrosis is characterised by deposition of collagen within the lung. The role of viral respiratory tract infections in IPF is unclear. The aim of this study is to investigate the role of viral infections in collagen deposition within the lung. C57Bl6 mice were infected with 20HAU influenza ‘x319 for 5 days or rhinovirus for 3,7 days or PBS. Lungs were harvested and a hydroxyproline (HYP) assay was performed. 60U of bleomycin were instilled into the lungs of C57Bl/6 mice to induce pulmonary fibrosis. After 28 days mice were exposed intranasally to 10, 20HAU influenza virus or PBS. Lungs were harvested 5 or 21 days later for mRNA analysis, histology and HYP levels. Mice with non-fibrotic lungs infected with influenza showed increased lung collagen deposition as early as 5 days post-infection. Mice infected with rhinovirus showed no increase in lung collagen levels 3 days or 7 days post-infection. Mice that were given bleomycin for 28 days showed an enhanced fibrotic response after influenza infection: there were increased lung HYP levels and an increase in matrix deposition on Masson9s trichrome. There also was an increase in CCNA2 mRNA in influenza-infected, bleomycin-exposed mice, indicating an increase in epithelial apoptosis. These data suggest that influenza infection promotes exacerbations of lung collagen deposition perhaps via epithelial cell apoptosis and TGFβ activation.