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Using human precision-cut lung slices (hPCLSs), primary human air\u2013liquid interface\u2013differentiated airway epithelial cells (HAECs), and human airway smooth muscle (HASM) as preclinical experimental models, we demonstrated that RV-C15 attenuates agonist-induced bronchodilation. Specifically, airway relaxation to formoterol and cholera toxin, but not forskolin (Fsk), was attenuated following hPCLS exposure to RV-C15. In isolated HASM cells, exposure to conditioned media from RV-exposed HAECs decreased cellular relaxation in response to isoproterenol and prostaglandin E2, but not Fsk. Additionally, cAMP generation elicited by formoterol and isoproterenol, but not Fsk, was attenuated following HASM exposure to RV-C15\u2013conditioned HAEC media. HASM exposure to RV-C15\u2013conditioned HAEC media modulated expression of components of relaxation pathways, specifically GNAI1 and GRK2. Strikingly, similar to exposure to intact RV-C15, hPCLS exposed to UV-inactivated RV-C15 showed markedly attenuated airway relaxation in response to formoterol, suggesting that the mechanism(s) of RV-C15\u2013mediated loss of bronchodilation is independent of virus replication pathways. Further studies are warranted to identify soluble factor(s) regulating the epithelial-driven smooth muscle loss of \u03b22-adrenergic receptor function.<\/jats:p>","DOI":"10.1165\/rcmb.2021-0526oc","type":"journal-article","created":{"date-parts":[[2023,4,25]],"date-time":"2023-04-25T14:11:32Z","timestamp":1682431892000},"page":"172-181","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":9,"title":["Rhinovirus C15 Attenuates Relaxation and cAMP Production in Human Airways and Smooth Muscle"],"prefix":"10.1093","volume":"69","author":[{"given":"Eric B.","family":"Gebski","sequence":"first","affiliation":[{"name":"Rutgers Institute for Translational Medicine and Science, New Brunswick, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishal","family":"Parikh","sequence":"additional","affiliation":[{"name":"Rutgers Institute for Translational Medicine and Science, New Brunswick, New 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