| Title: |
Stealth replication of SARS-CoV-2 Omicron in the nasal epithelium at physiological temperature |
| Authors: |
Fonseca, Bárbara; Robinot, Rémy; Michel, Vincent; Mendez, Akram; Lebourgeois, Samuel; Chivé, Chloé; Jeger-Madiot, Raphaël; Vaid, Roshan; Bondet, Vincent; Maloney, Elizabeth; Guivel-Benhassine, Florence; Schwartz, Olivier; Duffy, Darragh; Mondal, Tanmoy; Gobaa, Samy; Chakrabarti, Lisa |
| Contributors: |
Virus et immunité - Virus and immunity; Institut Pasteur Paris (IP)-Université Paris Cité (UPCité); Biomatériaux et Microfluidiques (plateforme) - Biomaterials and Microfluidics (platform); Pathogénèse des Infections vasculaires / Pathogenesis of Vascular Infections; Institut Pasteur Paris (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité); Göteborgs Universitet = University of Gothenburg (GU); Immunologie Translationnelle - Translational Immunology lab; Sahlgrenska University Hospital Gothenburg; This work was supported by the 3D-LUNGO project (reference ANRS-23-PEPR-MIE 0001) supported by the program France 2030 and managed by the French National Agency for AIDS and Emerging Diseases Research ANRS-MIE (to L.A.C. and S.G.); the COROCHIP project funded by the Institut Pasteur COVID-19 RP call (to L.A.C. and S.G.); the Tous Unis COVID project (reference PR-166156) funded by the Fondation de France (to L.A.C.); the PFR7 project funded by the Urgence COVID-19 Fundraising Campaign of Institut Pasteur (to L.A.C.); the PERSICOT project (reference ECTZ213626) funded by ANRS-MIE (to L.A.C.); the Steroid Response project funded by the Institut Pasteur COVID-19 RP call (to D.D.). R.R. was the recipient of a Sidaction fellowship, S.L. of an ANRS-MIE / Fondation pour la Recherche Médicale (FRM) fellowship, and C.C. of a France 2030 / ANRS-MIE PEPR fellowship. R.V. was funded by the Stiftelsen Clas Groschinskys Minnesfonds, grant number MF2576.; We thank Hugo Mouquet and Cyril Planchais (Humoral Immunity Unit, Institut Pasteur) for providing the Spike-specific antibody and Delphine Planas and Isabelle Staropoli (Virus & Immunity Unit, Institut Pasteur) for help with the infectivity experiments. We acknowledge the Photonic BioImaging UtechS, supported by the French National Research Agency (France BioImaging; ANR-10–INSB–04; Investments for the Future), for help with image acquisition and the Biomics core facility of Institut Pasteur for RNA integrity analysis.; ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010) |
| Source: |
ISSN: 0022-538X. |
| Publisher Information: |
CCSD; American Society for Microbiology |
| Publication Year: |
2025 |
| Subject Terms: |
SARS-CoV-2; mucosal immunity; motile cilia; interferon; nasal epithelium; MESH: Humans; MESH: Gastrointestinal Microbiome; MESH: Young Adult; MESH: Environment; MESH: Male; MESH: Female; MESH: Middle Aged; MESH: Adult; MESH: Bacteria; MESH: Aged; MESH: Healthy Volunteers; [SDV]Life Sciences [q-bio] |
| Description: |
International audience ; The COVID-19 pandemic was marked by successive waves of SARS-CoV-2 variants with distinct properties. The Omicron variant that emerged in late 2021 showed a major antigenic shift and rapidly spread worldwide. Since then, Omicron-derived variants have maintained their global dominance, for reasons that remain incompletely understood. We report that the original Omicron variant BA.1 evolved several traits that converged in facilitating viral spread. First, Omicron displayed an early replicative advantage over previous variants when grown in a reconstructed human nasal epithelium model. The increase in Omicron replication was more marked at the physiologically relevant temperature of 33°C found in human nasal passages. Omicron also caused a decrease in epithelial integrity, as measured by transepithelial electrical resistance and caspase-3 activation. Furthermore, Omicron caused a more marked loss of motile cilia at 33°C than other variants, suggesting a capacity to impair mucociliary clearance. Omicron induced a broad transcriptional downregulation of ciliary genes but only a limited upregulation of host innate defense genes at 33°C. The lower production of type I and type III interferons in epithelia infected by Omicron compared to those infected by the Delta variant, at 33°C as well as 37°C, confirmed the increased capacity of Omicron to evade the innate antiviral response. Thus, Omicron combined replication speed, motile cilia impairment, and limited induction of innate antiviral responses when propagated in nasal epithelia at physiological temperature. Omicron has the capacity to propagate rapidly but stealthily in the upper respiratory tract, which likely contributed to the evolutionary success of this SARS-CoV-2 variant.IMPORTANCEThe COVID-19 pandemic was initially characterized by a rapid succession of viral variants that emerged independently of each other, with each of these variants outcompeting the previous one. A major evolutionary shift occurred in late 2021, with the ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/41416837; PUBMED: 41416837 |
| DOI: |
10.1128/jvi.02008-25 |
| Availability: |
https://pasteur.hal.science/pasteur-05451173; https://pasteur.hal.science/pasteur-05451173v2/document; https://pasteur.hal.science/pasteur-05451173v2/file/fonseca-et-al-2025-stealth-replication-of-sars-cov-2-omicron-in-the-nasal-epithelium-at-physiological-temperature.pdf; https://doi.org/10.1128/jvi.02008-25 |
| Rights: |
http://creativecommons.org/licenses/by/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.A7CC9FE6 |
| Database: |
BASE |