{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:36:28Z","timestamp":1791203788449,"version":"4.2.0"},"reference-count":61,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2011,7]]},"abstract":"<jats:p> Both respiratory syncytial virus (RSV) and influenza A virus induce nucleotide\/P2Y purinergic receptor-mediated impairment of alveolar fluid clearance (AFC), which contributes to formation of lung edema. Although genetically dissimilar, both viruses generate double-stranded RNA replication intermediates, which act as Toll-like receptor (TLR)-3 ligands. We hypothesized that double-stranded RNA\/TLR-3 signaling underlies nucleotide-mediated inhibition of amiloride-sensitive AFC in both infections. We found that addition of the synthetic double-stranded RNA analog poly-inosinic-cytidylic acid [poly(I:C)] (500 ng\/ml) to the AFC instillate resulted in nucleotide\/P2Y purinergic receptor-mediated inhibition of amiloride-sensitive AFC in BALB\/c mice but had no effect on cystic fibrosis transmembrane regulator (CFTR)-mediated Cl<jats:sup>\u2212<\/jats:sup> transport. Poly(I:C) also induced acute keratinocyte cytokine-mediated AFC insensitivity to stimulation by the \u03b2-adrenergic agonist terbutaline. Inhibitory effects of poly(I:C) on AFC were absent in TLR-3<jats:sup>\u2212\/\u2212<\/jats:sup> mice and were not replicated by addition to the AFC instillate of ligands for other TLRs except TLR-2. Intranasal poly(I:C) administration (250 \u03bcg\/mouse) similarly induced nucleotide-dependent AFC inhibition 2\u20133 days later, together with increased lung water content and neutrophilic inflammation. Intranasal treatment of BALB\/c mice with poly(I:C) did not induce airway hyperresponsiveness at day 2 but did result in insensitivity to airway bronchodilation by \u03b2-adrenergic agonists. These findings suggest that viral double-stranded RNA replication intermediates induce nucleotide-mediated impairment of amiloride-sensitive AFC in both infections, together with \u03b2-adrenergic agonist insensitivity. Both of these effects also occur in RSV infection. However, double-stranded RNA replication intermediates do not appear to be sufficient to induce either adenosine-mediated, CFTR-dependent Cl<jats:sup>\u2212<\/jats:sup> secretion in the lung or severe, lethal hypoxemia, both of which are features of influenza infection. <\/jats:p>","DOI":"10.1152\/ajplung.00398.2010","type":"journal-article","created":{"date-parts":[[2011,4,9]],"date-time":"2011-04-09T01:54:45Z","timestamp":1302314085000},"page":"L99-L109","source":"Crossref","is-referenced-by-count":54,"title":["Double-stranded RNA induces similar pulmonary dysfunction to respiratory syncytial virus in BALB\/c mice"],"prefix":"10.1152","volume":"301","author":[{"given":"Famke","family":"Aeffner","sequence":"first","affiliation":[{"name":"Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary P.","family":"Traylor","sequence":"additional","affiliation":[{"name":"Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin N. 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