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The spike gene is a major determinant for the SARS-CoV-2 Omicron-BA.1 phenotype.
Barut, G Tuba; Halwe, Nico Joel; Taddeo, Adriano; Kelly, Jenna N; Schön, Jacob; Ebert, Nadine; Ulrich, Lorenz; Devisme, Christelle; Steiner, Silvio; Trüeb, Bettina Salome; Hoffmann, Bernd; Veiga, Inês Berenguer; Leborgne, Nathan Georges François; Moreira, Etori Aguiar; Breithaupt, Angele; Wylezich, Claudia; Höper, Dirk; Wernike, Kerstin; Godel, Aurélie; Thomann, Lisa; Flück, Vera; Stalder, Hanspeter; Brügger, Melanie; Esteves, Blandina I Oliveira; Zumkehr, Beatrice; Beilleau, Guillaume; Kratzel, Annika; Schmied, Kimberly; Ochsenbein, Sarah; Lang, Reto M; Wider, Manon; Machahua, Carlos; Dorn, Patrick; Marti, Thomas M; Funke-Chambour, Manuela; Rauch, Andri; Widera, Marek; Ciesek, Sandra; Dijkman, Ronald; Hoffmann, Donata; Alves, Marco P; Benarafa, Charaf; Beer, Martin; Thiel, Volker.
  • Barut GT; Institute of Virology and Immunology, Bern and Mittelhäusern, Bern, Switzerland.
  • Halwe NJ; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
  • Taddeo A; Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Greifswald, Germany.
  • Kelly JN; Institute of Virology and Immunology, Bern and Mittelhäusern, Bern, Switzerland.
  • Schön J; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
  • Ebert N; Institute of Virology and Immunology, Bern and Mittelhäusern, Bern, Switzerland.
  • Ulrich L; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
  • Devisme C; Multidisciplinary Center for Infectious Diseases, University of Bern, Bern, Switzerland.
  • Steiner S; European Virus Bioinformatics Center, Jena, Germany.
  • Trüeb BS; Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Greifswald, Germany.
  • Hoffmann B; Institute of Virology and Immunology, Bern and Mittelhäusern, Bern, Switzerland.
  • Veiga IB; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
  • Leborgne NGF; Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Greifswald, Germany.
  • Moreira EA; Institute of Virology and Immunology, Bern and Mittelhäusern, Bern, Switzerland.
  • Breithaupt A; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
  • Wylezich C; Institute of Virology and Immunology, Bern and Mittelhäusern, Bern, Switzerland.
  • Höper D; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
  • Wernike K; Institute of Virology and Immunology, Bern and Mittelhäusern, Bern, Switzerland.
  • Godel A; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
  • Thomann L; Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Greifswald, Germany.
  • Flück V; Institute of Virology and Immunology, Bern and Mittelhäusern, Bern, Switzerland.
  • Stalder H; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
  • Brügger M; Institute of Virology and Immunology, Bern and Mittelhäusern, Bern, Switzerland.
  • Esteves BIO; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
  • Zumkehr B; Institute of Virology and Immunology, Bern and Mittelhäusern, Bern, Switzerland.
  • Beilleau G; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
  • Kratzel A; Department of Experimental Animal Facilities and Biorisk Management, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Greifswald, Germany.
  • Schmied K; Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Greifswald, Germany.
  • Ochsenbein S; Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Greifswald, Germany.
  • Lang RM; Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Greifswald, Germany.
  • Wider M; Institute of Virology and Immunology, Bern and Mittelhäusern, Bern, Switzerland.
  • Machahua C; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
  • Dorn P; Institute of Virology and Immunology, Bern and Mittelhäusern, Bern, Switzerland.
  • Marti TM; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
  • Funke-Chambour M; Institute of Virology and Immunology, Bern and Mittelhäusern, Bern, Switzerland.
  • Rauch A; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
  • Widera M; Institute of Virology and Immunology, Bern and Mittelhäusern, Bern, Switzerland.
  • Ciesek S; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
  • Dijkman R; Institute of Virology and Immunology, Bern and Mittelhäusern, Bern, Switzerland.
  • Hoffmann D; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
  • Alves MP; Institute of Virology and Immunology, Bern and Mittelhäusern, Bern, Switzerland.
  • Benarafa C; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
  • Beer M; Institute of Virology and Immunology, Bern and Mittelhäusern, Bern, Switzerland.
  • Thiel V; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
Nat Commun ; 13(1): 5929, 2022 10 07.
Article in English | MEDLINE | ID: covidwho-2062208
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Type of study: Experimental Studies Topics: Vaccines / Variants Limits: Animals / Humans Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2022 Document Type: Article Affiliation country: S41467-022-33632-y

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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Type of study: Experimental Studies Topics: Vaccines / Variants Limits: Animals / Humans Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2022 Document Type: Article Affiliation country: S41467-022-33632-y