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The mechanisms underpinning this increased susceptibility to infection in COPD are unclear. In this study, we show that primary bronchial epithelial cells (pBECs) from subjects with COPD have impaired induction of type I IFN (IFN-\u03b2) and lead to heightened viral replication after influenza viral infection. COPD pBECs have reduced protein levels of protein kinase (PK) R and decreased formation of PKR-mediated antiviral stress granules, which are critical in initiating type I IFN inductions. In addition, reduced protein expression of p300 resulted in decreased activation of IFN regulatory factor 3 and subsequent formation of IFN-\u03b2 enhanceosome in COPD pBECs. The decreased p300 induction was the result of enhanced levels of microRNA (miR)-132. Ectopic expression of PKR or miR-132 antagomiR alone failed to restore IFN-\u03b2 induction, whereas cotreatment increased antiviral stress granule formation, induction of p300, and IFN-\u03b2 in COPD pBECs. This study reveals that decreased induction of both PKR and p300 proteins contribute to impaired induction of IFN-\u03b2 in COPD pBECs upon influenza infection.<\/jats:p>","DOI":"10.1165\/rcmb.2015-0306oc","type":"journal-article","created":{"date-parts":[[2016,1,25]],"date-time":"2016-01-25T16:05:56Z","timestamp":1453737956000},"page":"117-127","source":"Crossref","is-referenced-by-count":50,"title":["Impaired Antiviral Stress Granule and IFN-\u03b2 Enhanceosome Formation Enhances Susceptibility to Influenza Infection in Chronic Obstructive Pulmonary Disease Epithelium"],"prefix":"10.1093","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6640-0846","authenticated-orcid":false,"given":"Alan C.-Y.","family":"Hsu","sequence":"first","affiliation":[{"name":"Priority Research Centre for Asthma and Respiratory Disease, Hunter Medical Research Institute, The University of Newcastle, Newcastle, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristy","family":"Parsons","sequence":"additional","affiliation":[{"name":"Priority Research Centre for Asthma and Respiratory Disease, Hunter Medical Research Institute, The University of Newcastle, Newcastle, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Moheimani","sequence":"additional","affiliation":[{"name":"Priority Research Centre for Asthma and Respiratory Disease, Hunter Medical Research Institute, The University of Newcastle, Newcastle, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darryl A.","family":"Knight","sequence":"additional","affiliation":[{"name":"Priority Research Centre for Asthma and Respiratory Disease, Hunter Medical Research Institute, The University of Newcastle, Newcastle, New South Wales, Australia"},{"name":"Department of Anesthesiology, Pharmacology, and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip M.","family":"Hansbro","sequence":"additional","affiliation":[{"name":"Priority Research Centre for Asthma and Respiratory Disease, Hunter Medical Research Institute, The University of Newcastle, Newcastle, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Fujita","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics, Institute for Virus Research, Kyoto University, Kyoto, Japan; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A.","family":"Wark","sequence":"additional","affiliation":[{"name":"Priority Research Centre for Asthma and Respiratory Disease, Hunter Medical Research Institute, The University of Newcastle, Newcastle, New South Wales, Australia"},{"name":"Department of Respiratory and Sleep Medicine, John Hunter Hospital, New 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