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Surfactant protein A (SP-A) plays a critical role in regulating pulmonary innate immunity by binding to numerous respiratory pathogens. Mature SP-A consists of multiple isoforms that form the hetero-oligomers of SP-A1 and SP-A2, organized in 18-mers. In this report, we examined the efficacy of SP-A to antagonize RV-C infection using the wild-type (RV-C15) and reporter-expressing (RV-C15-GFP) viruses in differentiated nasal epithelial cells (NECs) from asthmatic and non-asthmatic children. We also determined the antiviral mechanism of action of SP-A on RV-C15 infection. The native SP-A was purified from alveolar proteinosis patients. The recombinant (r) SP-A1 and SP-A2 variants were expressed in FreeStyle\u2122 293-F cells. SP-A reduced the fluorescent focus-forming units (FFUs) after RV-C15-GFP infection of NECs by 99%. Both simultaneous and 4 h post-infection treatment with SP-A inhibited RV-C15 and RV-C15-GFP viral RNA load by 97%. In addition, the antiviral genes and chemokines (IFN-\u03bb, IRF-7, MDA-5, and CXLC11) were not induced in the infected NECs due to the inhibition of RV-C propagation by SP-A. Furthermore, SP-A bound strongly to RV-C15 in a dose- and Ca2+-dependent manner, and this interaction inhibited RV-C15 binding to NECs. In contrast, rSP-A1 did not bind to solid-phase RV-C15, whereas the rSP-A2 variants, [A91, K223] and [P91, Q223], had strong binding affinities to RV-C15, similar to native SP-A. This study demonstrates that SP-A might have potential as an antiviral for RV infection and RV-induced asthma exacerbations.<\/jats:p>","DOI":"10.3390\/v16111709","type":"journal-article","created":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T06:55:37Z","timestamp":1730357737000},"page":"1709","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Surfactant Protein A Inhibits Human Rhinovirus C Binding and Infection of Airway Epithelial Cells from Pediatric Asthma"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2188-5990","authenticated-orcid":false,"given":"Sasipa","family":"Tanyaratsrisakul","sequence":"first","affiliation":[{"name":"Department of Medicine, National Jewish Health, Denver, CO 80206, USA"},{"name":"Asthma and Airway Disease Research Center, University of Arizona, Tucson, AZ 85724, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2618-4496","authenticated-orcid":false,"given":"Yury A.","family":"Bochkov","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5500-4098","authenticated-orcid":false,"given":"Vanessa","family":"White","sequence":"additional","affiliation":[{"name":"Department of Medicine, National Jewish Health, Denver, CO 80206, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heejung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Medicine, National Jewish Health, Denver, CO 80206, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Loeffler","sequence":"additional","affiliation":[{"name":"Department of Medicine, National Jewish Health, Denver, CO 80206, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie","family":"Everman","sequence":"additional","affiliation":[{"name":"Center for Genes, Environment and Health, National Jewish Health, Denver, CO 80206, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison M.","family":"Schiltz","sequence":"additional","affiliation":[{"name":"Section of Pediatric Pulmonary & Sleep Medicine, Children\u2019s Hospital Colorado and University of Colorado School of Medicine, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristy L.","family":"Freeman","sequence":"additional","affiliation":[{"name":"Section of Pediatric Pulmonary & Sleep Medicine, Children\u2019s Hospital Colorado and University of Colorado School of Medicine, Aurora, CO 80045, 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Wei","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Medicine, National Jewish Health, Denver, CO 80206, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew H.","family":"Liu","sequence":"additional","affiliation":[{"name":"Section of Pediatric Pulmonary & Sleep Medicine, Children\u2019s Hospital Colorado and University of Colorado School of Medicine, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7977-4575","authenticated-orcid":false,"given":"Julie G.","family":"Ledford","sequence":"additional","affiliation":[{"name":"Asthma and Airway Disease Research Center, University of Arizona, Tucson, AZ 85724, USA"},{"name":"Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ 85719, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Kraft","sequence":"additional","affiliation":[{"name":"Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max A.","family":"Seibold","sequence":"additional","affiliation":[{"name":"Center for Genes, Environment and Health, National Jewish Health, Denver, CO 80206, USA"},{"name":"Department of Pediatrics, National Jewish Health, Denver, CO 80206, USA"},{"name":"Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado-AMC, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis R.","family":"Voelker","sequence":"additional","affiliation":[{"name":"Department of Medicine, National Jewish Health, Denver, CO 80206, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6310-6801","authenticated-orcid":false,"given":"Mari","family":"Numata","sequence":"additional","affiliation":[{"name":"Department of Medicine, National Jewish Health, Denver, CO 80206, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1164\/rccm.200802-309OC","article-title":"Wheezing rhinovirus illnesses in early life predict asthma development in high-risk children","volume":"178","author":"Jackson","year":"2008","journal-title":"Am. 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