The Impact of Influenza Infection on the Lung Transcriptome During Repair

Seasonal and pandemic influenza is a cause of morbidity and mortality worldwide. Most people infected with influenza virus display mild to moderate disease phenotypes and recover within a few weeks. Influenza is known to cause persistent alveolitis in animal models, however little is known about the molecular pathways involved in this phenotype. We challenged C57BL/6 mice with influenza A/PR/8/34 and examined lung pathology and inflammation, as well as transcriptomic and epigenetic changes at 21 to 60 days post-infection. Influenza induced persistent parenchymal lung inflammation, alveolar epithelial metaplasia, and epithelial endoplasmic reticulum stress that were evident following the clearance of virus and resolution of morbidity. Influenza infection induced robust changes in the lung transcriptome including a significant impact on inflammatory and extracellular matrix protein expression. We analyzed 16 samples of whole lung RNA from mice infected with influenza (FLU, A/PR/8/34) or with vehicle control (PBS). Samples were collected at 21 and 35 days post-infection. All samples were run twice, thus producing technical replicates for each sample.