ArticleProceedings of the National Academy of Sciences of the United States of America2022
Bronchial epithelia from adults and children: SARS-CoV-2 spread via syncytia formation and type III interferon infectivity restriction.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 31 citations in OpenAlex.
- Viral syncytia evolve to resist interferon.Nature communications · 2026Article
- Review
- Differential Induction and Signaling of Type I and III Interferons During Infection of Human Nasal Epithelial Cells With the Four Human Parainfluenza Virus Types.Journal of medical virology · 2026Article
- From models to medicine: systematic development and evaluation of animal models forFrontiers in immunology · 2026Review
- Article
- SARS-CoV-2 spike treatment and transfection impairs airway epithelial repair.ERJ open research · 2025Article
- Utilizing Nanopore direct RNA sequencing of blood from patients with sepsis for discovery of co- and post-transcriptional disease biomarkers.BMC infectious diseases · 2025Article
- Cell Culture Differentiation and Proliferation Conditions Influence theAmerican journal of respiratory cell and molecular biology · 2024Article
- Intranasal adenovirus-vectored Omicron vaccine induced nasal immunoglobulin A has superior neutralizing potency than serum antibodies.Signal transduction and targeted therapy · 2024Article
- Uncovering strain- and age-dependent innate immune responses to SARS-CoV-2 infection in air-liquid-interface cultured nasal epithelia.iScience · 2024Article
- Age-specific nasal epithelial responses to SARS-CoV-2 infection.Nature microbiology · 2024Article
- Diverging patterns in innate immunity against respiratory viruses during a lifetime: lessons from the young and the old.European respiratory review : an official journal of the European Respiratory Society · 2024Review
- Virus-Induced Cell Fusion and Syncytia Formation.Results and problems in cell differentiation · 2024Article
- Early immune profiling reveals distinct inflammatory responses between children and adults few days after primary SARS-CoV-2 infection.Frontiers in immunology · 2024Article
- Smoke and Spike: Benzo[a]pyrene Enhances SARS-CoV-2 Infection by Boosting NR4A2-Induced ACE2 and TMPRSS2 Expression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Review
- Human airway and nasal organoids reveal escalating replicative fitness of SARS-CoV-2 emerging variants.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Potential of Interferon Lambda as an Inhibitor of SARS-CoV-2.Molecular biology · 2023Article
- Spike protein mediated membrane fusion during SARS-CoV-2 infection.Journal of medical virology · 2023Review
- Ganoderma microsporum immunomodulatory protein acts as a multifunctional broad-spectrum antiviral against SARS-CoV-2 by interfering virus binding to the host cells and spike-mediated cell fusion.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2022Article
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Authors and funding
20 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections initiate in the bronchi of the upper respiratory tract and are able to disseminate to the lower respiratory tract, where infections can cause an acute respiratory distress syndrome with a high degree of mortality in elderly patients. We used reconstituted primary bronchial epithelia from adult and child donors to follow the SARS-CoV-2 infection dynamics. We show that, in epithelia from adult donors, infections initiate in multiciliated cells and spread within 24 to 48 h throughout the whole epithelia. Syncytia formed of ciliated and basal cells appeared at the apical side of the epithelia within 3 to 4 d and were released into the apical lumen, where they contributed to the transmittable virus dose. A small number of reconstituted epithelia were intrinsically more resistant to virus infection, limiting virus spread to different degrees. This phenotype was more frequent in epithelia derived from children versus adults and correlated with an accelerated release of type III interferon. Treatment of permissive adult epithelia with exogenous type III interferon restricted infection, while type III interferon gene knockout promoted infection. Furthermore, a transcript analysis revealed that the inflammatory response was specifically attenuated in children. Taken together, our findings suggest that apical syncytia formation is an underappreciated source of virus propagation for tissue or environmental dissemination, whereas a robust type III interferon response such as commonly seen in young donors restricted SARS-CoV-2 infection. Thus, the combination of interferon restriction and attenuated inflammatory response in children might explain the epidemiological observation of age-related susceptibility to COVID-19.
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