ArticleThe Journal of allergy and clinical immunology2019
Functional genomics of CDHR3 confirms its role in HRV-C infection and childhood asthma exacerbations.
Article in The Journal of allergy and clinical immunology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 108 citations in OpenAlex.
- Treatment by biomarker-informed endotype vs guideline care in children with difficult-to-treat asthma.Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology · 2022Trial
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- Tonic and early interferons defend against respiratory viruses in primary human lung organoid-derived air-liquid interface cultures.Journal of virology · 2026Article
- A robust cell-based infection model for Rhinovirus C research and antiviral drug discovery.Npj viruses · 2026Article
- Unique nasal cell states induced by common pediatric respiratory viruses.bioRxiv : the preprint server for biology · 2026Article
- Stability and age-specific patterns of rhinovirus circulation in children observed over 3 decades.The Journal of allergy and clinical immunology · 2026Article
- Broad-spectrum host-targeting antivirals for rhinovirus infections: mechanisms and future perspectives.Frontiers in immunology · 2026Review
- Article
- The role of virus in nasal inflammation.European journal of medical research · 2025Review
- Risk Factors and Mechanisms Leading to Preschool Recurrent Wheeze and Asthma.The journal of allergy and clinical immunology. In practice · 2025Review
- Genetic Susceptibility to Acute Viral Bronchiolitis.The Journal of infectious diseases · 2025Article
- Independent association of a 17q21 variant with exacerbations in type 2-low adult asthma.The journal of allergy and clinical immunology. Global · 2025Article
- The PRIMERO birth cohort: Design and baseline characteristics.The journal of allergy and clinical immunology. Global · 2025Article
- Clinical Significance of Rhinoviruses and Progress Toward Vaccination.Allergy, asthma & immunology research · 2025Review
- Association between cadherin-related family member 3 rs6967330-A and human rhinovirus-C induced wheezing in children.Virology journal · 2025Article
- The rs6967330 minor allele in CDHR3 is a significant risk factor for severe acute exacerbations in chronic rhinosinusitis.The Journal of allergy and clinical immunology · 2025Article
- Surfactant Protein A Inhibits Human Rhinovirus C Binding and Infection of Airway Epithelial Cells from Pediatric Asthma.Viruses · 2024Article
- Human Stimulator of Interferon Genes Promotes Rhinovirus C Replication in Mouse Cells In Vitro and In Vivo.Viruses · 2024Article
- Effect of air pollution on asthma.Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology · 2024Review
- Adjuvant-independent airway sensitization and infection mouse models leading to allergic asthma.Frontiers in allergy · 2024Review
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundResearch in transformed immortalized cell lines indicates the cadherin-related family member 3 (CDHR3) protein serves as a receptor for human rhinovirus (HRV)-C. Similar experiments indicate that the CDHR3 coding variant rs6967330 increases CDHR3 protein surface expression.
objectiveWe sought to determine whether CDHR3 is necessary for HRV-C infection of primary airway epithelial cells (AECs) and to identify molecular mechanisms by which CDHR3 variants confer risk for asthma exacerbations.
methodsCDHR3 function and influence on HRV-C infection were investigated by using single-cell transcriptomics, CRISPR-Cas9 gene knockout, and genotype-specific donor experiments performed in primary AECs. Nasal airway epithelium cis-expression quantitative trait locus (eQTL) analysis of CDHR3 was performed, followed by association testing for asthma hospitalization in minority children.
resultsCDHR3 lung expression is exclusive to ciliated AECs and associated with basal bodies during and after motile ciliogenesis. Knockout of CDHR3 in human AECs did not prevent ciliated cell differentiation but was associated with a decrease in transepithelial resistance and an 80% decrease in HRV-C infection of the mucociliary epithelium. AECs from subjects homozygous for the risk-associated rs6967330 single nucleotide polymorphism (SNP) exhibited greater HRV-C infection compared with cells homozygous for the nonrisk allele. AEC cis-eQTL analysis indicated that rs6967330 and other SNPs are eQTLs for CDHR3. Only the eQTL block containing the rs6967330 SNP showed a significant association with childhood asthma hospitalization.
conclusionsGenetic deletion and genotype-specific studies in primary AECs indicate CDHR3 is critical to HRV-C infection of ciliated cells. The rs6967330 SNP confers risk of severe childhood asthma exacerbations, likely through increasing HRV-C infection levels and protein surface localization.
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