Abstract
Introduction: Human rhinovirus(RV-A16) plays a major role in exacerbation of asthma. However, there are limited studies revealing metabolic changes in this process. We compare metabolic response in primary airway epithelium from patients with asthma and controls when stimulated with RV-A16 to reveal possible relevance to pathogenesis of virus-induced asthma exacerbations.
Methods: We stimulated primary bronchial epithelial cells in air-liquid interphase or monolayer with RV-A16, then examined gene, protein and functional metabolic changes by RNA-seq, qPCR, targeted proteomics, and Seahorse analysis. We also analysed microarray data from the bronchial brushings of patients with asthma and control infected with RV-A16.
Results: We found that OXPHOS genes were upregulated in epithelial cells of asthmatics and controls after infection. But there were more OXPHOS genes uniquely downregulated in asthmatics. In line with gene expression data, we observed higher totalATP rates in controls after infection. In addition, we found that more genes encoding glycolysis pathway were uniquely upregulated in the epithelial cells from asthmatics. Interestingly, in vivo study indicated many OXPHOS and glycolysis genes were uniquely downregulated in controls at 4 days post RV-A16 infection, but remained unchanged in patients with asthma.
Conclusions: Rhinovirus infection in asthmatics leads to less pronounced mitochondrial respiration may suggest less efficient antiviral response. In contrast, enhanced glycolysis may support viral replication in those patients. Only healthy controls actively suppress energy production at later infection stage may indicate resolution of inflammation.
Footnotes
Cite this article as Eur Respir J 2022; 60: Suppl. 66, LSC-0200.
This article was presented at the 2022 ERS International Congress, in session “-”.
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).
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