SARS-CoV-2 leverages airway epithelial protective mechanism for viral infection.
iScience. 2023 Mar 17; 26(3):106175.I

Abstract

Despite much concerted effort to better understand severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection, relatively little is known about the dynamics of early viral entry and infection in the airway. Here we analyzed a single-cell RNA sequencing dataset of early SARS-CoV-2 infection in a humanized in vitro model, to elucidate key mechanisms by which the virus triggers a cell-systems-level response in the bronchial epithelium. We find that SARS-CoV-2 virus preferentially enters the tissue via ciliated cell precursors, giving rise to a population of infected mature ciliated cells, which signal to basal cells, inducing further rapid differentiation. This feedforward loop of infection is mitigated by further cell-cell communication, before interferon signaling begins at three days post-infection. These findings suggest hijacking by the virus of potentially beneficial tissue repair mechanisms, possibly exacerbating the outcome. This work both elucidates the interplay between barrier tissues and viral infections and may suggest alternative therapeutic approaches targeting non-immune response mechanisms.

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Authors+Show Affiliations

Greaney AM

Department of Biomedical Engineering, Yale University, New Haven, CT 06511, USA. Vascular Biology and Therapeutics Program, Yale School of Medicine, New Haven, CT 06511, USA.

Raredon MSB

Department of Biomedical Engineering, Yale University, New Haven, CT 06511, USA. Vascular Biology and Therapeutics Program, Yale School of Medicine, New Haven, CT 06511, USA. Medical Scientist Training Program, Yale University, New Haven, CT 06511, USA.

Kochugaeva MP

Department of Biomedical Engineering, Yale University, New Haven, CT 06511, USA. Yale Systems Biology Institute, Yale University, West Haven, CT 06516, USA.

Niklason LE

Department of Biomedical Engineering, Yale University, New Haven, CT 06511, USA. Vascular Biology and Therapeutics Program, Yale School of Medicine, New Haven, CT 06511, USA. Department of Anesthesiology, Yale School of Medicine, New Haven, CT 06510, USA. Humacyte Inc., Durham, NC 27713, USA.

Levchenko A

Department of Biomedical Engineering, Yale University, New Haven, CT 06511, USA. Yale Systems Biology Institute, Yale University, West Haven, CT 06516, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

36788793

Citation

Greaney, Allison Marie, et al. "SARS-CoV-2 Leverages Airway Epithelial Protective Mechanism for Viral Infection." IScience, vol. 26, no. 3, 2023, p. 106175.

Greaney AM, Raredon MSB, Kochugaeva MP, et al. SARS-CoV-2 leverages airway epithelial protective mechanism for viral infection. iScience. 2023;26(3):106175.

Greaney, A. M., Raredon, M. S. B., Kochugaeva, M. P., Niklason, L. E., & Levchenko, A. (2023). SARS-CoV-2 leverages airway epithelial protective mechanism for viral infection. IScience, 26(3), 106175. https://doi.org/10.1016/j.isci.2023.106175

Greaney AM, et al. SARS-CoV-2 Leverages Airway Epithelial Protective Mechanism for Viral Infection. iScience. 2023 Mar 17;26(3):106175. PubMed PMID: 36788793.

* Article titles in AMA citation format should be in sentence-case

TY - JOUR T1 - SARS-CoV-2 leverages airway epithelial protective mechanism for viral infection. AU - Greaney,Allison Marie, AU - Raredon,Micha Sam Brickman, AU - Kochugaeva,Maria P, AU - Niklason,Laura E, AU - Levchenko,Andre, Y1 - 2023/02/10/ PY - 2022/03/11/received PY - 2023/01/05/revised PY - 2023/02/03/accepted PY - 2023/2/16/pubmed PY - 2023/2/16/medline PY - 2023/2/15/entrez KW - Biological sciences KW - Immunology KW - Transcriptomics KW - Virology SP - 106175 EP - 106175 JF - iScience JO - iScience VL - 26 IS - 3 N2 - Despite much concerted effort to better understand severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection, relatively little is known about the dynamics of early viral entry and infection in the airway. Here we analyzed a single-cell RNA sequencing dataset of early SARS-CoV-2 infection in a humanized in vitro model, to elucidate key mechanisms by which the virus triggers a cell-systems-level response in the bronchial epithelium. We find that SARS-CoV-2 virus preferentially enters the tissue via ciliated cell precursors, giving rise to a population of infected mature ciliated cells, which signal to basal cells, inducing further rapid differentiation. This feedforward loop of infection is mitigated by further cell-cell communication, before interferon signaling begins at three days post-infection. These findings suggest hijacking by the virus of potentially beneficial tissue repair mechanisms, possibly exacerbating the outcome. This work both elucidates the interplay between barrier tissues and viral infections and may suggest alternative therapeutic approaches targeting non-immune response mechanisms. SN - 2589-0042 UR - https://www.unboundmedicine.com/medline/citation/36788793/SARS_CoV_2_leverages_airway_epithelial_protective_mechanism_for_viral_infection_ DB - PRIME DP - Unbound Medicine ER -

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SARS-CoV-2 leverages airway epithelial protective mechanism for viral infection.iScience. 2023 Mar 17; 26(3):106175.I