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The spike gene is a major determinant for the SARS-CoV-2 Omicron-BA.1 phenotype
Tuba Barut; Nico Joel Halwe; Adriano Taddeo; Jenna N. Kelly; Jacob Schön; Nadine Ebert; Lorenz Ulrich; Christelle Devisme; Silvio Steiner; Bettina Salome Trueeb; Bernd Hoffmann; Inês Berenguer Veiga; Nathan François Georges Leborgne; Etori Aquiar 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; Volker Thiel.
Afiliação
  • Tuba Barut; Institute of Virology and Immunology, Bern and Mittelhäusern, Switzerland; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of
  • Nico Joel Halwe; Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany
  • Adriano Taddeo; Institute of Virology and Immunology, Bern and Mittelhäusern, Switzerland; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of
  • Jenna N. Kelly; Institute of Virology and Immunology, Bern, Switzerland; Department of Infectious Diseases and Pathobiology; Multidisciplinary Center for Infectious Diseases, U
  • Jacob Schön; Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany
  • Nadine Ebert; Institute of Virology and Immunology, Bern and Mittelhäusern, Switzerland; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of
  • Lorenz Ulrich; Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany
  • Christelle Devisme; Institute of Virology and Immunology, Bern and Mittelhäusern, Switzerland; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of
  • Silvio Steiner; Institute of Virology and Immunology, Bern and Mittelhäusern, Switzerland; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of
  • Bettina Salome Trueeb; Institute of Virology and Immunology, Bern and Mittelhäusern, Switzerland; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of
  • Bernd Hoffmann; Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany
  • Inês Berenguer Veiga; Institute of Virology and Immunology, Bern and Mittelhäusern, Switzerland; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of
  • Nathan François Georges Leborgne; Institute of Virology and Immunology, Bern and Mittelhäusern, Switzerland; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of
  • Etori Aquiar Moreira; Institute of Virology and Immunology, Bern and Mittelhäusern, Switzerland; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of
  • Angele Breithaupt; Department of Experimental Animal Facilities and Biorisk Management, Friedrich-LoefflerInstitut, Greifswald-Insel Riems, Germany
  • Claudia Wylezich; Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany
  • Dirk Höper; Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany
  • Kerstin Wernike; Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany
  • Aurélie Godel; Institute of Virology and Immunology, Bern and Mittelhäusern, Switzerland; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of
  • Lisa Thomann; Institute of Virology and Immunology, Bern and Mittelhäusern, Switzerland; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of
  • Vera Flück; Institute of Virology and Immunology, Bern and Mittelhäusern, Switzerland; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of
  • Hanspeter Stalder; Institute of Virology and Immunology, Bern and Mittelhäusern, Switzerland; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of
  • Melanie Brügger; Institute of Virology and Immunology, Bern and Mittelhäusern, Switzerland; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of
  • Blandina I. Oliveira Esteves; Institute of Virology and Immunology, Bern and Mittelhäusern, Switzerland; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of
  • Beatrice Zumkehr; Institute of Virology and Immunology, Bern and Mittelhäusern, Switzerland; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of
  • Guillaume Beilleau; Institute of Virology and Immunology, Bern and Mittelhäusern, Switzerland; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of
  • Annika Kratzel; Institute of Virology and Immunology, Bern and Mittelhäusern, Switzerland; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of
  • Kimberly Schmied; Institute of Virology and Immunology, Bern and Mittelhäusern, Switzerland; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of
  • Sarah Ochsenbein; Institute of Virology and Immunology, Bern and Mittelhäusern, Switzerland; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of
  • Reto M. Lang; Institute of Virology and Immunology, Bern and Mittelhäusern, Switzerland; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of
  • Manon Wider; Institute for Infectious Diseases, University of Bern, Bern, Switzerland
  • Carlos Machahua; Department of Pulmonary Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; Department for Pulmonary Medicine, BioMedical Re
  • Patrick Dorn; Division of General Thoracic Surgery, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; Department for BioMedical Research, Inselspi
  • Thomas M. Marti; Division of General Thoracic Surgery, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; Department for BioMedical Research, Inselspi
  • Manuela Funke-Chambour; Department of Pulmonary Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; Department for Pulmonary Medicine, BioMedical Re
  • Andri Rauch; Multidisciplinary Center for Infectious Diseases, University of Bern, Bern, Switzerland; Department of Infectious Diseases, Inselspital, Bern University Hospita
  • Marek Widera; Institute of Medical Virology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany
  • Sandra Ciesek; Institute of Medical Virology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany
  • Ronald Dijkman; Multidisciplinary Center for Infectious Diseases, University of Bern, Bern, Switzerland; European Virus Bioinformatics Center, Jena, Germany; Institute for Infe
  • Donata Hoffmann; Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany
  • Marco P Alves; Institute of Virology and Immunology, Bern and Mittelhäusern, Switzerland; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, Bern, Switzerl
  • Charaf Benarafa; Institute of Virology and Immunology, Bern and Mittelhäusern, Switzerland; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, Bern, Switzerl
  • Martin Beer; Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany; European Virus Bioinformatics Center, Jena, Germany
  • Volker Thiel; Institute of Virology and Immunology, Bern; Department of Infectious Diseases and Pathobiology. Bern; Multidisciplinary Center for Infectious Diseases, Universi
Preprint em Inglês | bioRxiv | ID: ppbiorxiv-489537
ABSTRACT
Variant of concern (VOC) Omicron-BA1 has achieved global predominance in early 2022. Therefore, surveillance and comprehensive characterization of Omicron-BA.1 in advanced primary cell culture systems and multiple animal models is urgently needed. Here, we characterized 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 naive hamsters, ferrets and hACE2-expressing mice, and in 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 Syrian hamsters, Delta showed dominance over Omicron-BA.1 and in ferrets, Omicron-BA.1 infection was abortive. In mice expressing the authentic hACE2-receptor, Delta and a Delta spike clone also showed dominance over Omicron-BA.1 and an Omicron-BA.1 spike clone, respectively. Interestingly, in naive K18-hACE2 mice, we observed 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 both Delta and Omicron-BA.1 replication and pathogenicity. Finally, the Omicron-BA.1 spike clone was less well controlled by mRNA-vaccination in K18-hACE2-mice and became 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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Texto completo: Disponível Coleções: Preprints Base de dados: bioRxiv Tipo de estudo: Experimental_studies Idioma: Inglês Ano de publicação: 2022 Tipo de documento: Preprint
Texto completo
Adicionar na Minha BVS
Imprimir
XML
Buscar no Google
Texto completo: Disponível Coleções: Preprints Base de dados: bioRxiv Tipo de estudo: Experimental_studies Idioma: Inglês Ano de publicação: 2022 Tipo de documento: Preprint