Enhanced fitness of SARS-CoV-2 variant of concern Alpha but not Beta.

Ulrich, Lorenz; Halwe, Nico Joel; Taddeo, Adriano; Ebert, Nadine; Schön, Jacob; Devisme, Christelle; Trüeb, Bettina Salome; Hoffmann, Bernd; Wider, Manon; Fan, Xiaoyu; Bekliz, Meriem; Essaidi-Laziosi, Manel; Schmidt, Marie Luisa; Niemeyer, Daniela; Corman, Victor Max; Kraft, Anna; Godel, Aurélie; Laloli, Laura; Kelly, Jenna N; Calderon, Brenda M; ... (2022). Enhanced fitness of SARS-CoV-2 variant of concern Alpha but not Beta. Nature, 602(7896), pp. 307-313. Springer Nature 10.1038/s41586-021-04342-0

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Emerging variants of concern (VOC) drive the SARS-CoV-2 pandemic1,2. Experimental assessment of replication and transmission of major VOC compared to progenitors are needed to understand successful emerging mechanisms of VOC3. Here, we show that Alpha and Beta spike (S) proteins have a greater affinity to human angiotensin converting enzyme 2 (hACE2) receptor over the progenitor variant (wt-S614G) in vitro. Yet Alpha and wt-S614G had similar replication kinetics in human nasal airway epithelial cultures, whereas Beta was outcompeted by both. In vivo, competition experiments showed a clear fitness advantage of Alpha over the progenitor variant (wt-S614G) in ferrets and two mouse models, where the substitutions in S were major drivers for fitness advantage. In hamsters, supporting high replication levels, Alpha and wt-S614G had comparable fitness. In contrast, Beta was outcompeted by Alpha and wt-S614G in hamsters and hACE2-expressing mice. Our study highlights the importance of using multiple models for complete fitness characterization of VOC and demonstrates adaptation of Alpha towards increased upper respiratory tract replication and enhanced transmission in vivo in restrictive models, whereas Beta fails to overcome contemporary strains in naïve animals.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases > Research
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Virology and Immunology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Veterinary Bacteriology

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Taddeo, Adriano; Ebert, Nadine; Devisme, Christelle; Trüeb, Bettina Salome; Wider, Manon Flore; Godel, Aurélie; Laloli, Laura; Kelly, Jenna Nicole; Gultom, Mitra Lovelin; Thomann, Lisa Jane; Gsell-Albert, Monika; Labroussaa, Fabien; Jores, Jörg; Summerfield, Artur; Dijkman, Ronald; Thiel, Volker Earl and Benarafa, Charaf

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health
600 Technology > 630 Agriculture

ISSN:

1476-4687

Publisher:

Springer Nature

Language:

English

Submitter:

Siegfried Hektor Hapfelmeier-Balmer

Date Deposited:

24 Jan 2022 12:18

Last Modified:

24 Jun 2022 00:25

Publisher DOI:

10.1038/s41586-021-04342-0

PubMed ID:

34937050

Additional Information:

Ronald Dijkman, Donata Hoffmann, Volker Thiel, Martin Beer & Charaf Benarafa are co-last authors as described authors description in the published paper

BORIS DOI:

10.48350/163848

URI:

https://boris.unibe.ch/id/eprint/163848

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