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 and 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:

18 May 2021 11:01

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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