Omicron subvariants illustrate reduced respiratory tissue penetration, cell damage and inflammatory responses in human airway epithelia

Frontiers in Immunology

Immunology

Lukas A. Huber¹  Wilfried Posch²  Hussam Abd El Halim²  Viktoria Zaderer²  Doris Wilflingseder²  Cornelia Lass-Flörl²  Anna-Lena Wyremblewsky²  Helmut Blum³  Alexander Graf³  Maximilian Muenchhoff⁴  Gaia Lupoli⁴  Oliver T. Keppler⁴  Christopher Dächert⁴ 

[1] Institute of Cell Biology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria;ADSI - Austrian Drug Screening Institute GmbH, Innsbruck, Austria;Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria;Laboratory for Functional Genome Analysis, Gene Center, Ludwig-Maximilians-Universität (LMU), Munich, Germany;Virology, Max von Pettenkofer Institute and Gene Center, Ludwig-Maximilians-Universität (LMU), Munich, Germany;

关键词: SARS-CoV-2;    VOCs;    delta;    omicron;    epithelial barrier model;   

DOI  :  10.3389/fimmu.2023.1258268

 received in 2023-07-13, accepted in 2023-10-02,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionTo explore whether the reported lower pathogenicity in infected individuals of variant of concern (VoC) Omicron and its current subvariants compared to VoC Delta may be related to fundamental differences in the initial virus-tissue interaction, we assessed their ability to penetrate, replicate and cause damage in a human 3D respiratory model.MethodsFor this, we used TEER measurements, real-time PCR, LDH, cytokine and complex confocal imaging analyses.Results and discussionWe observed that Delta readily penetrated deep into the respiratory epithelium and this was associated with major tissue destruction, high LDH activity, high viral loads and pronounced innate immune activation as observed by intrinsic C3 activation and IL-6 release at infection sites. In contrast, Omicron subvariants BA.5, BQ.1.1 and BF7 remained superficially in the mucosal layer resulting merely in outward-directed destruction of cells, maintenance of epithelial integrity, minimal LDH activity and low basolateral release of virus at infection sites, as well as significantly smaller areas of complement activation and lower IL-6 secretion. Interestingly, also within Omicron subvariants differences were observed with newer Omicron subvariants BQ.1.1 and BF.7 illustrating significantly reduced viral loads, IL-6 release and LDH activity compared to BA.5. Our data indicate that earliest interaction events after SARS-CoV-2 transmission may have a role in shaping disease severity.

【 授权许可】

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Copyright © 2023 Zaderer, Abd El Halim, Wyremblewsky, Lupoli, Dächert, Muenchhoff, Graf, Blum, Lass-Flörl, Keppler, Huber, Posch and Wilflingseder