Enhanced fitness of SARS-CoV-2 variant of concern Alpha but not Beta
Lorenz Ulrich,
Nico Joel Halwe,
Adriano Taddeo,
Nadine Ebert,
Jacob Schön,
Christelle Devisme,
Bettina Salome Trüeb,
Bernd Hoffmann,
Manon Wider,
Xiaoyu Fan,
Meriem Bekliz,
Manel Essaidi-Laziosi,
Marie Luisa Schmidt,
Daniela Niemeyer,
Victor Max Corman,
Anna Kraft,
Aurélie Godel,
Laura Laloli,
Jenna N. Kelly,
Brenda M. Calderon,
Angele Breithaupt,
Claudia Wylezich,
Inês Berenguer Veiga,
Mitra Gultom,
Sarah Osman,
Bin Zhou,
Kenneth Adea,
Benjamin Meyer,
Christiane S. Eberhardt,
Lisa Thomann,
Monika Gsell,
Fabien Labroussaa,
Jörg Jores,
Artur Summerfield,
Christian Drosten,
Isabella Anne Eckerle,
David E. Wentworth,
Ronald Dijkman,
Donata Hoffmann,
Volker Thiel (),
Martin Beer () and
Charaf Benarafa ()
Additional contact information
Lorenz Ulrich: Friedrich-Loeffler-Institut
Nico Joel Halwe: Friedrich-Loeffler-Institut
Adriano Taddeo: Institute of Virology and Immunology
Nadine Ebert: Institute of Virology and Immunology
Jacob Schön: Friedrich-Loeffler-Institut
Christelle Devisme: Institute of Virology and Immunology
Bettina Salome Trüeb: Institute of Virology and Immunology
Bernd Hoffmann: Friedrich-Loeffler-Institut
Manon Wider: University of Bern
Xiaoyu Fan: Centers for Disease Control and Prevention
Meriem Bekliz: University of Geneva
Manel Essaidi-Laziosi: University of Geneva
Marie Luisa Schmidt: Charité–Universitätsmedizin Berlin, Institute of Virology
Daniela Niemeyer: Charité–Universitätsmedizin Berlin, Institute of Virology
Victor Max Corman: Charité–Universitätsmedizin Berlin, Institute of Virology
Anna Kraft: Friedrich-Loeffler-Institut
Aurélie Godel: Institute of Virology and Immunology
Laura Laloli: University of Bern
Jenna N. Kelly: Institute of Virology and Immunology
Brenda M. Calderon: Centers for Disease Control and Prevention
Angele Breithaupt: Friedrich-Loeffler-Institut
Claudia Wylezich: Friedrich-Loeffler-Institut
Inês Berenguer Veiga: Institute of Virology and Immunology
Mitra Gultom: University of Bern
Sarah Osman: Centers for Disease Control and Prevention
Bin Zhou: Centers for Disease Control and Prevention
Kenneth Adea: University of Geneva
Benjamin Meyer: University of Geneva
Christiane S. Eberhardt: University of Geneva
Lisa Thomann: Institute of Virology and Immunology
Monika Gsell: University of Bern
Fabien Labroussaa: Institute of Veterinary Bacteriology, Vetsuisse Faculty, University of Bern
Jörg Jores: Institute of Veterinary Bacteriology, Vetsuisse Faculty, University of Bern
Artur Summerfield: Institute of Virology and Immunology
Christian Drosten: Charité–Universitätsmedizin Berlin, Institute of Virology
Isabella Anne Eckerle: University of Geneva
David E. Wentworth: Centers for Disease Control and Prevention
Ronald Dijkman: University of Bern
Donata Hoffmann: Friedrich-Loeffler-Institut
Volker Thiel: Institute of Virology and Immunology
Martin Beer: Friedrich-Loeffler-Institut
Charaf Benarafa: Institute of Virology and Immunology
Nature, 2022, vol. 602, issue 7896, 307-313
Abstract:
Abstract Emerging variants of concern (VOCs) are driving the COVID-19 pandemic1,2. Experimental assessments of replication and transmission of major VOCs and progenitors are needed to understand the mechanisms of replication and transmission of VOCs3. Here we show that the spike protein (S) from Alpha (also known as B.1.1.7) and Beta (B.1.351) VOCs had a greater affinity towards the human angiotensin-converting enzyme 2 (ACE2) receptor than that of the progenitor variant S(D614G) in vitro. Progenitor variant virus expressing S(D614G) (wt-S614G) and the Alpha variant showed similar replication kinetics in human nasal airway epithelial cultures, whereas the Beta variant was outcompeted by both. In vivo, competition experiments showed a clear fitness advantage of Alpha over wt-S614G in ferrets and two mouse models—the substitutions in S were major drivers of the fitness advantage. In hamsters, which support high viral replication levels, Alpha and wt-S614G showed similar fitness. By contrast, Beta was outcompeted by Alpha and wt-S614G in hamsters and in mice expressing human ACE2. Our study highlights the importance of using multiple models to characterize fitness of VOCs and demonstrates that Alpha is adapted for replication in the upper respiratory tract and shows enhanced transmission in vivo in restrictive models, whereas Beta does not overcome Alpha or wt-S614G in naive animals.
Date: 2022
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DOI: 10.1038/s41586-021-04342-0
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