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The spike gene is a major determinant for the SARS-CoV-2 Omicron-BA.1 phenotype

Author

Listed:
  • G. Tuba Barut

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern)

  • Nico Joel Halwe

    (Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems)

  • Adriano Taddeo

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern)

  • Jenna N. Kelly

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern
    University of Bern
    European Virus Bioinformatics Center)

  • Jacob Schön

    (Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems)

  • Nadine Ebert

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern)

  • Lorenz Ulrich

    (Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems)

  • Christelle Devisme

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern)

  • Silvio Steiner

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern)

  • Bettina Salome Trüeb

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern)

  • Bernd Hoffmann

    (Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems)

  • Inês Berenguer Veiga

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern)

  • Nathan Georges François Leborgne

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern)

  • Etori Aguiar Moreira

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern)

  • Angele Breithaupt

    (Friedrich-Loeffler-Institut, Greifswald-Insel Riems)

  • Claudia Wylezich

    (Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems)

  • Dirk Höper

    (Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems)

  • Kerstin Wernike

    (Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems)

  • Aurélie Godel

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern)

  • Lisa Thomann

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern)

  • Vera Flück

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern)

  • Hanspeter Stalder

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern)

  • Melanie Brügger

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern)

  • Blandina I. Oliveira Esteves

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern)

  • Beatrice Zumkehr

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern)

  • Guillaume Beilleau

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern
    University of Bern)

  • Annika Kratzel

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern)

  • Kimberly Schmied

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern)

  • Sarah Ochsenbein

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern)

  • Reto M. Lang

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern
    University of Bern)

  • Manon Wider

    (University of Bern)

  • Carlos Machahua

    (Bern University Hospital, University of Bern
    University of Bern)

  • Patrick Dorn

    (Bern University Hospital, University of Bern
    Bern University Hospital, University of Bern)

  • Thomas M. Marti

    (Bern University Hospital, University of Bern
    Bern University Hospital, University of Bern)

  • Manuela Funke-Chambour

    (Bern University Hospital, University of Bern
    University of Bern)

  • Andri Rauch

    (University of Bern
    Bern University Hospital, University of Bern)

  • Marek Widera

    (University Hospital Frankfurt, Goethe University)

  • Sandra Ciesek

    (University Hospital Frankfurt, Goethe University)

  • Ronald Dijkman

    (University of Bern
    European Virus Bioinformatics Center
    University of Bern)

  • Donata Hoffmann

    (Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems)

  • Marco P. Alves

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern
    University of Bern)

  • Charaf Benarafa

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern
    University of Bern)

  • Martin Beer

    (Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems
    European Virus Bioinformatics Center)

  • Volker Thiel

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern
    University of Bern
    European Virus Bioinformatics Center)

Abstract

Variant of concern (VOC) Omicron-BA.1 has achieved global predominance in early 2022. Therefore, surveillance and comprehensive characterization of Omicron-BA.1 in advanced primary cell culture systems and animal models are urgently needed. Here, we characterize Omicron-BA.1 and recombinant Omicron-BA.1 spike gene mutants in comparison with VOC Delta in well-differentiated primary human nasal and bronchial epithelial cells in vitro, followed by in vivo fitness characterization in hamsters, ferrets and hACE2-expressing mice, and immunized hACE2-mice. We demonstrate a spike-mediated enhancement of early replication of Omicron-BA.1 in nasal epithelial cultures, but limited replication in bronchial epithelial cultures. In hamsters, Delta shows dominance over Omicron-BA.1, and in ferrets Omicron-BA.1 infection is abortive. In hACE2-knock-in mice, Delta and a Delta spike clone also show dominance over Omicron-BA.1 and an Omicron-BA.1 spike clone, respectively. Interestingly, in naïve K18-hACE2 mice, we observe Delta spike-mediated increased replication and pathogenicity and Omicron-BA.1 spike-mediated reduced replication and pathogenicity, suggesting that the spike gene is a major determinant of replication and pathogenicity. Finally, the Omicron-BA.1 spike clone is less well-controlled by mRNA-vaccination in K18-hACE2-mice and becomes more competitive compared to the progenitor and Delta spike clones, suggesting that spike gene-mediated immune evasion is another important factor that led to Omicron-BA.1 dominance.

Suggested Citation

  • G. Tuba Barut & Nico Joel Halwe & Adriano Taddeo & Jenna N. Kelly & Jacob Schön & Nadine Ebert & Lorenz Ulrich & Christelle Devisme & Silvio Steiner & Bettina Salome Trüeb & Bernd Hoffmann & Inês Bere, 2022. "The spike gene is a major determinant for the SARS-CoV-2 Omicron-BA.1 phenotype," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33632-y
    DOI: 10.1038/s41467-022-33632-y
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    1. Markus Hoffmann & Lok-Yin Roy Wong & Prerna Arora & Lu Zhang & Cheila Rocha & Abby Odle & Inga Nehlmeier & Amy Kempf & Anja Richter & Nico Joel Halwe & Jacob Schön & Lorenz Ulrich & Donata Hoffmann & , 2023. "Omicron subvariant BA.5 efficiently infects lung cells," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    2. Taha Y. Taha & Irene P. Chen & Jennifer M. Hayashi & Takako Tabata & Keith Walcott & Gabriella R. Kimmerly & Abdullah M. Syed & Alison Ciling & Rahul K. Suryawanshi & Hannah S. Martin & Bryan H. Bach , 2023. "Rapid assembly of SARS-CoV-2 genomes reveals attenuation of the Omicron BA.1 variant through NSP6," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

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