Enhanced fitness of SARS-CoV-2 variant of concern Alpha but not Beta.
Autor: | Ulrich L; Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany., Halwe NJ; Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany., Taddeo A; Institute of Virology and Immunology, Mittelhäusern, Switzerland.; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland., Ebert N; Institute of Virology and Immunology, Mittelhäusern, Switzerland.; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland., Schön J; Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany., Devisme C; Institute of Virology and Immunology, Mittelhäusern, Switzerland.; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland., Trüeb BS; Institute of Virology and Immunology, Mittelhäusern, Switzerland.; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.; Institute of Veterinary Bacteriology, Vetsuisse Faculty, University of Bern, Bern, Switzerland., Hoffmann B; Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany., Wider M; Institute for Infectious Diseases, University of Bern, Bern, Switzerland., Fan X; CDC COVID-19 Emergency Response, Centers for Disease Control and Prevention, Atlanta, GA, USA., Bekliz M; Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland., Essaidi-Laziosi M; Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland., Schmidt ML; Charité-Universitätsmedizin Berlin, Institute of Virology, Berlin, Germany., Niemeyer D; Charité-Universitätsmedizin Berlin, Institute of Virology, Berlin, Germany.; German Centre for Infection Research (DZIF), Berlin, Germany., Corman VM; Charité-Universitätsmedizin Berlin, Institute of Virology, Berlin, Germany.; German Centre for Infection Research (DZIF), Berlin, Germany., Kraft A; Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany., Godel A; Institute of Virology and Immunology, Mittelhäusern, Switzerland.; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland., Laloli L; Institute for Infectious Diseases, University of Bern, Bern, Switzerland.; Graduate School for Biomedical Science, University of Bern, Bern, Switzerland., Kelly JN; Institute of Virology and Immunology, Mittelhäusern, Switzerland.; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland., Calderon BM; CDC COVID-19 Emergency Response, Centers for Disease Control and Prevention, Atlanta, GA, USA., Breithaupt A; Department of Experimental Animal Facilities and Biorisk Management, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany., Wylezich C; Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany., Berenguer Veiga I; Institute of Virology and Immunology, Mittelhäusern, Switzerland.; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland., Gultom M; Institute for Infectious Diseases, University of Bern, Bern, Switzerland.; Graduate School for Biomedical Science, University of Bern, Bern, Switzerland., Osman S; CDC COVID-19 Emergency Response, Centers for Disease Control and Prevention, Atlanta, GA, USA., Zhou B; CDC COVID-19 Emergency Response, Centers for Disease Control and Prevention, Atlanta, GA, USA., Adea K; Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland., Meyer B; Centre for Vaccinology, Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland., Eberhardt CS; Centre for Vaccinology, Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.; Division of General Paediatrics, Department of Woman, Child and Adolescent Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland.; Center for Vaccinology, Geneva University Hospitals, Geneva, Switzerland., Thomann L; Institute of Virology and Immunology, Mittelhäusern, Switzerland.; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland., Gsell M; Institute for Infectious Diseases, University of Bern, Bern, Switzerland., Labroussaa F; Institute of Veterinary Bacteriology, Vetsuisse Faculty, University of Bern, Bern, Switzerland., Jores J; Institute of Veterinary Bacteriology, Vetsuisse Faculty, University of Bern, Bern, Switzerland., Summerfield A; Institute of Virology and Immunology, Mittelhäusern, Switzerland.; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland., Drosten C; Charité-Universitätsmedizin Berlin, Institute of Virology, Berlin, Germany.; German Centre for Infection Research (DZIF), Berlin, Germany., Eckerle IA; Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland.; Division of Infectious Disease, Geneva University Hospitals, Geneva, Switzerland.; Division of Laboratory Medicine, Laboratory of Virology, Geneva University Hospitals, Geneva, Switzerland., Wentworth DE; CDC COVID-19 Emergency Response, Centers for Disease Control and Prevention, Atlanta, GA, USA., Dijkman R; Institute for Infectious Diseases, University of Bern, Bern, Switzerland., Hoffmann D; Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany., Thiel V; Institute of Virology and Immunology, Mittelhäusern, Switzerland. volker.thiel@vetsuisse.unibe.ch.; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland. volker.thiel@vetsuisse.unibe.ch., Beer M; Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany. martin.beer@fli.de., Benarafa C; Institute of Virology and Immunology, Mittelhäusern, Switzerland. charaf.benarafa@vetsuisse.unibe.ch.; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland. charaf.benarafa@vetsuisse.unibe.ch. |
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Jazyk: | angličtina |
Zdroj: | Nature [Nature] 2022 Feb; Vol. 602 (7896), pp. 307-313. Date of Electronic Publication: 2021 Dec 22. |
DOI: | 10.1038/s41586-021-04342-0 |
Abstrakt: | Emerging variants of concern (VOCs) are driving the COVID-19 pandemic 1,2 . Experimental assessments of replication and transmission of major VOCs and progenitors are needed to understand the mechanisms of replication and transmission of VOCs 3 . 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-S 614G ) 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-S 614G 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-S 614G showed similar fitness. By contrast, Beta was outcompeted by Alpha and wt-S 614G 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-S 614G in naive animals. (© 2021. The Author(s).) |
Databáze: | MEDLINE |
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