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Epigenetic and Transcriptomic Regulation of Lung Repair during Recovery from Influenza Infection

tetano

Editor, Senior Moderator
Am J Pathol. 2017 Feb 9. pii: S0002-9440(17)30062-7. doi: 10.1016/j.ajpath.2016.12.012. [Epub ahead of print]
[h=1]Epigenetic and Transcriptomic Regulation of Lung Repair during Recovery from Influenza Infection.[/h] Pociask DA[SUP]1[/SUP], Robinson KM[SUP]2[/SUP], Chen K[SUP]3[/SUP], McHugh KJ[SUP]4[/SUP], Clay ME[SUP]4[/SUP], Huang GT[SUP]5[/SUP], Benos PV[SUP]6[/SUP], Janssen-Heininger YM[SUP]7[/SUP], Kolls JK[SUP]3[/SUP], Anathy V[SUP]8[/SUP], Alcorn JF[SUP]9[/SUP].
[h=3]Author information[/h]

[h=3]Abstract[/h] 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 pathologic processes and inflammation, as well as transcriptomic and epigenetic changes at 21 to 60 days after infection. Influenza induced persistent parenchymal lung inflammation, alveolar epithelial metaplasia, and epithelial endoplasmic reticulum stress that were evident after 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. Despite the robust changes in lung gene expression, preceding influenza (21 days) did not exacerbate secondary Staphylococcus aureus infection. Finally, we examined the impact of influenza on miRNA expression in the lung and found an increase in miR-155. miR-155 knockout mice recovered from influenza infection faster than controls and had decreased lung inflammation and endoplasmic reticulum stress. These data illuminate the dynamic molecular changes in the lung in the weeks after influenza infection and characterize the repair process, identifying a novel role for miR-155.
Copyright ? 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.


PMID: 28193481 DOI: 10.1016/j.ajpath.2016.12.012
[PubMed - as supplied by publisher]
 
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