Surfactant Protein A Inhibits Human Rhinovirus C Binding and Infection of Airway Epithelial Cells from Pediatric Asthma
Abstract
Rhinovirus C (RV-C) infection can trigger asthma exacerbations in children and adults, and RV-C-induced wheezing illnesses in preschool children correlate with the development of childhood asthma. 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™ 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-λ, 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.
Related
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BibTeX
@article{tanyaratsrisakul2026surfactant,
title = {{Surfactant Protein A Inhibits Human Rhinovirus C Binding and Infection of Airway Epithelial Cells from Pediatric Asthma}},
author = {S. Tanyaratsrisakul and Y. A. Bochkov and V. White and H. Lee and J. Loeffler and J. Everman and A. M. Schiltz and K. L. Freeman and K. L. Hamlington and E. A. Secor and N. D. Jackson and H. W. Chu and A. H. Liu and J. G. Ledford and M. Kraft and M. A. Seibold and D. R. Voelker and M. Numata},
journal = {Viruses},
year = {2026},
month = oct,
doi = {10.3390/v16111709},
url = {https://hal.science/hal-05787899v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Surfactant Protein A Inhibits Human Rhinovirus C Binding and Infection of Airway Epithelial Cells from Pediatric Asthma
AU - S. Tanyaratsrisakul
AU - Y. A. Bochkov
AU - V. White
AU - H. Lee
AU - J. Loeffler
AU - J. Everman
AU - A. M. Schiltz
AU - K. L. Freeman
AU - K. L. Hamlington
AU - E. A. Secor
AU - N. D. Jackson
AU - H. W. Chu
AU - A. H. Liu
AU - J. G. Ledford
AU - M. Kraft
AU - M. A. Seibold
AU - D. R. Voelker
AU - M. Numata
PY - 2026
DA - 2026/10/09
JO - Viruses
DO - 10.3390/v16111709
UR - https://hal.science/hal-05787899v1
AB - Rhinovirus C (RV-C) infection can trigger asthma exacerbations in children and adults, and RV-C-induced wheezing illnesses in preschool children correlate with the development of childhood asthma. 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™ 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-λ, 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.
SN - 1999-4915
ER -