Surfactant Protein A Inhibits Human Rhinovirus C Binding and Infection of Airway Epithelial Cells from Pediatric Asthma

• Published in: Viruses 2024-10, Vol.16 (11), p.1709
• Main Authors: Tanyaratsrisakul, Sasipa, Bochkov, Yury A, White, Vanessa, Lee, Heejung, Loeffler, Jessica, Everman, Jamie, Schiltz, Allison M, Freeman, Kristy L, Hamlington, Katharine L, Secor, Elizabeth A, Jackson, Nathan D, Chu, Hong Wei, Liu, Andrew H, Ledford, Julie G, Kraft, Monica, Seibold, Max A, Voelker, Dennis R, Numata, Mari
• Format: Article
• Language: English
• Subjects: Airway management; Alveoli; Antiviral activity; Antiviral agents; Asthma; Asthma - metabolism; Asthma - virology; Asthma in children; Calcium; Cell differentiation; Chemokines; Child; Child, Preschool; Children; Complications and side effects; Development and progression; Dosage and administration; Drug therapy; Enterovirus - genetics; Enterovirus - physiology; Epithelial cells; Epithelial Cells - metabolism; Epithelial Cells - virology; Genes; human rhinovirus C; Humans; Infections; Innate immunity; Interferon regulatory factor 7; Isoforms; Molecular weight; pediatric asthma; Pediatrics; Picornaviridae Infections - metabolism; Picornaviridae Infections - virology; Proteins; pulmonary surfactant protein A; Pulmonary Surfactant-Associated Protein A - genetics; Pulmonary Surfactant-Associated Protein A - metabolism; Respiratory diseases; Rhinovirus; Rhinovirus - physiology; Rhinovirus C; Rhinoviruses; Risk factors; Surface active agents; Surfactant protein A; Surfactants; Testing; Viral infections; Virus Attachment - drug effects; Viruses; Wheezing
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v16111709

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 Ca -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, [A , K ] and [P , Q ], 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.