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

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 Berenguer Veiga, Nathan Georges François Leborgne, Etori Aguiar Moreira, Angele Breithaupt, Claudia Wylezich, Dirk Höper, Kerstin Wernike, Aurélie Godel, Lisa Thomann, Vera Flück, Hanspeter Stalder, Melanie Brügger, Blandina I. Oliveira Esteves, Beatrice Zumkehr, Guillaume Beilleau, Annika Kratzel, Kimberly Schmied, Sarah Ochsenbein, Reto M. Lang, Manon Wider, Carlos Machahua, Patrick Dorn, Thomas M. Marti, Manuela Funke-Chambour, Andri Rauch, Marek Widera, Sandra Ciesek, Ronald Dijkman, Donata Hoffmann, Marco P. Alves (), Charaf Benarafa (), Martin Beer () and Volker Thiel ()
Additional contact information
G. Tuba Barut: Institute of Virology and Immunology, Bern and Mittelhäusern
Nico Joel Halwe: Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems
Adriano Taddeo: Institute of Virology and Immunology, Bern and Mittelhäusern
Jenna N. Kelly: Institute of Virology and Immunology, Bern and Mittelhäusern
Jacob Schön: Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems
Nadine Ebert: Institute of Virology and Immunology, Bern and Mittelhäusern
Lorenz Ulrich: Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems
Christelle Devisme: Institute of Virology and Immunology, Bern and Mittelhäusern
Silvio Steiner: Institute of Virology and Immunology, Bern and Mittelhäusern
Bettina Salome Trüeb: Institute of Virology and Immunology, Bern and Mittelhäusern
Bernd Hoffmann: Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems
Inês Berenguer Veiga: Institute of Virology and Immunology, Bern and Mittelhäusern
Nathan Georges François Leborgne: Institute of Virology and Immunology, Bern and Mittelhäusern
Etori Aguiar Moreira: Institute of Virology and Immunology, Bern and Mittelhäusern
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
Lisa Thomann: Institute of Virology and Immunology, Bern and Mittelhäusern
Vera Flück: Institute of Virology and Immunology, Bern and Mittelhäusern
Hanspeter Stalder: Institute of Virology and Immunology, Bern and Mittelhäusern
Melanie Brügger: Institute of Virology and Immunology, Bern and Mittelhäusern
Blandina I. Oliveira Esteves: Institute of Virology and Immunology, Bern and Mittelhäusern
Beatrice Zumkehr: Institute of Virology and Immunology, Bern and Mittelhäusern
Guillaume Beilleau: Institute of Virology and Immunology, Bern and Mittelhäusern
Annika Kratzel: Institute of Virology and Immunology, Bern and Mittelhäusern
Kimberly Schmied: Institute of Virology and Immunology, Bern and Mittelhäusern
Sarah Ochsenbein: Institute of Virology and Immunology, Bern and Mittelhäusern
Reto M. Lang: Institute of Virology and Immunology, Bern and Mittelhäusern
Manon Wider: University of Bern
Carlos Machahua: Bern University Hospital, University of Bern
Patrick Dorn: Bern University Hospital, University of Bern
Thomas M. Marti: Bern University Hospital, University of Bern
Manuela Funke-Chambour: Bern University Hospital, University of Bern
Andri Rauch: University of Bern
Marek Widera: University Hospital Frankfurt, Goethe University
Sandra Ciesek: University Hospital Frankfurt, Goethe University
Ronald Dijkman: 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
Charaf Benarafa: Institute of Virology and Immunology, Bern and Mittelhäusern
Martin Beer: Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems
Volker Thiel: Institute of Virology and Immunology, Bern and Mittelhäusern

Nature Communications, 2022, vol. 13, issue 1, 1-14

Abstract: 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.

Date: 2022
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Citations: View citations in EconPapers (3)

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DOI: 10.1038/s41467-022-33632-y

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