TY - JOUR T1 - LSC - 2019 - RNA degradation is a deficient antiviral mechanism in the asthmatic airway epithelium JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2019.PA5436 VL - 54 IS - suppl 63 SP - PA5436 AU - Taowen Wong AU - Jennifer Rynne AU - Peter H Howarth AU - Michael R Edwards AU - Rocio Teresa Martinez-Nunez Y1 - 2019/09/28 UR - http://erj.ersjournals.com/content/54/suppl_63/PA5436.abstract N2 - Background: Common cold (rhinovirus, RV) infections are the most frequent trigger of asthma exacerbations. Asthma is a common chronic inflammatory disease of the airways. Asthmatics show interferon-deficient responses to RV; however, the mechanisms underlying increased RV-driven symptoms leading to exacerbations are inadequately understood.Aim: To determine the role of RNA processing in antiviral immunity in asthma.Methods: We applied Frac-seq (subcellular fractionation and RNA-seq) in primary bronchial epithelial cells (BECs) from asthmatics and healthy controls. Frac-seq determines which cytoplasmic mRNAs bind to polyribosomes, the cellular translational machinery. We employed RNA immunoprecipitation (RIP) and siRNA knock-down experiments in bronchial epithelial cells (BEAS-2B) infected with RV1C.Results: Frac-seq data showed decreased translation of UPF1 (upstream frameshift 1) in asthma BECs. UPF1 translational levels negatively correlated with reversibility (r=-0.7235 P=0.0067). UPF1 is the main mediator of nonsense mediated decay (NMD), an RNA surveillance pathway that degrades potentially deleterious mRNAs (e.g. mRNAs with premature termination codons) and postulated to regulate 10-30% of all mRNAs. Emetine (a translation inhibitor that leads to upregulation of NMD targets) resulted in increased RV RNA levels. RIP showed that UPF1 directly binds RV RNA. Depletion of UPF1 in bronchial epithelial cells resulted in deficient RV-induced interferon (beta and lambda) and genome-wide changes in antiviral responses.Conclusions: Our data suggest that decreased UPF1 levels in asthma BECs contribute to impaired antiviral immunity and RV-induced exacerbations in asthma.FootnotesCite this article as: European Respiratory Journal 2019; 54: Suppl. 63, PA5436.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only). ER -