SARS-CoV-2 spike D614G change enhances replication and transmission

Zhou, Bin; Tran, Thi Nhu Thao; Hoffmann, Donata; Taddeo, Adriano; Ebert, Nadine; Labroussaa, Fabien; Pohlmann, Anne; King, Jacqueline; Steiner, Silvio; Kelly, Jenna N.; Portmann, Jasmine; Halwe, Nico Joel; Ulrich, Lorenz; Trüeb, Bettina Salome; Fan, Xiaoyu; Hoffmann, Bernd; Wang, Li; Thomann, Lisa; Lin, Xudong; Stalder, Hanspeter; ... (2021). SARS-CoV-2 spike D614G change enhances replication and transmission. Nature, 592(7852), pp. 122-127. Springer Nature 10.1038/s41586-021-03361-1

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During the evolution of SARS-CoV-2 in humans, a D614G substitution in the spike glycoprotein (S) has emerged; virus containing this substitution has become the predominant circulating variant in the COVID-19 pandemic1. However, whether the increasing prevalence of this variant reflects a fitness advantage that improves replication and/or transmission in humans or is merely due to founder effects remains unknown. Here we use isogenic SARS-CoV-2 variants to demonstrate that the variant that contains S(D614G) has enhanced binding to the human cell-surface receptor angiotensin-converting enzyme 2 (ACE2), increased replication in primary human bronchial and nasal airway epithelial cultures as well as in a human ACE2 knock-in mouse model, and markedly increased replication and transmissibility in hamster and ferret models of SARS-CoV-2 infection. Our data show that the D614G substitution in S results in subtle increases in binding and replication in vitro, and provides a real competitive advantage in vivo-particularly during the transmission bottleneck. Our data therefore provide an explanation for the global predominance of the variant that contains S(D614G) among the SARS-CoV-2 viruses that are currently circulating.

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 Animal Pathology
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
08 Faculty of Science > Department of Biology > Institute of Cell Biology

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Tran, Thi Nhu Thao, Taddeo, Adriano, Ebert, Nadine, Labroussaa, Fabien, Steiner, Silvio, Kelly, Jenna Nicole, Portmann, Jasmine, Trüeb, Bettina Salome, Thomann, Lisa Jane, Stalder, Hanspeter, Pozzi, Maria Berta, De Brot, Simone Danielle, Dijkman, Ronald, Jores, Jörg, Benarafa, Charaf, Thiel, Volker Earl

Subjects:

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

ISSN:

1476-4687

Publisher:

Springer Nature

Language:

English

Submitter:

Tran TN Thao

Date Deposited:

18 May 2021 11:01

Last Modified:

05 Dec 2022 15:51

Publisher DOI:

10.1038/s41586-021-03361-1

PubMed ID:

33636719

BORIS DOI:

10.48350/156281

URI:

https://boris.unibe.ch/id/eprint/156281

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