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

Author

Listed:
  • Bin Zhou

    (CDC COVID-19 Response, Centers for Disease Control and Prevention)

  • Tran Thi Nhu Thao

    (Institute of Virology and Immunology (IVI)
    University of Bern
    University of Bern)

  • Donata Hoffmann

    (Friedrich-Loeffler-Institut)

  • Adriano Taddeo

    (Institute of Virology and Immunology (IVI)
    University of Bern)

  • Nadine Ebert

    (Institute of Virology and Immunology (IVI)
    University of Bern)

  • Fabien Labroussaa

    (University of Bern
    University of Bern)

  • Anne Pohlmann

    (Friedrich-Loeffler-Institut)

  • Jacqueline King

    (Friedrich-Loeffler-Institut)

  • Silvio Steiner

    (Institute of Virology and Immunology (IVI)
    University of Bern
    University of Bern)

  • Jenna N. Kelly

    (Institute of Virology and Immunology (IVI)
    University of Bern)

  • Jasmine Portmann

    (Institute of Virology and Immunology (IVI)
    University of Bern)

  • Nico Joel Halwe

    (Friedrich-Loeffler-Institut)

  • Lorenz Ulrich

    (Friedrich-Loeffler-Institut)

  • Bettina Salome Trüeb

    (University of Bern
    University of Bern)

  • Xiaoyu Fan

    (CDC COVID-19 Response, Centers for Disease Control and Prevention)

  • Bernd Hoffmann

    (Friedrich-Loeffler-Institut)

  • Li Wang

    (CDC COVID-19 Response, Centers for Disease Control and Prevention)

  • Lisa Thomann

    (Institute of Virology and Immunology (IVI)
    University of Bern)

  • Xudong Lin

    (Battelle Memorial Institute)

  • Hanspeter Stalder

    (Institute of Virology and Immunology (IVI)
    University of Bern)

  • Berta Pozzi

    (University of Bern)

  • Simone Brot

    (University of Bern)

  • Nannan Jiang

    (Oak Ridge Institute for Science and Education)

  • Dan Cui

    (Battelle Memorial Institute)

  • Jaber Hossain

    (CDC COVID-19 Response, Centers for Disease Control and Prevention)

  • Malania M. Wilson

    (CDC COVID-19 Response, Centers for Disease Control and Prevention)

  • Matthew W. Keller

    (CDC COVID-19 Response, Centers for Disease Control and Prevention)

  • Thomas J. Stark

    (CDC COVID-19 Response, Centers for Disease Control and Prevention)

  • John R. Barnes

    (CDC COVID-19 Response, Centers for Disease Control and Prevention)

  • Ronald Dijkman

    (Institute of Virology and Immunology (IVI)
    University of Bern
    University of Bern)

  • Joerg Jores

    (University of Bern
    University of Bern)

  • Charaf Benarafa

    (Institute of Virology and Immunology (IVI)
    University of Bern)

  • David E. Wentworth

    (CDC COVID-19 Response, Centers for Disease Control and Prevention)

  • Volker Thiel

    (Institute of Virology and Immunology (IVI)
    University of Bern)

  • Martin Beer

    (Friedrich-Loeffler-Institut)

Abstract

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.

Suggested Citation

  • Bin Zhou & Tran Thi Nhu Thao & Donata Hoffmann & Adriano Taddeo & Nadine Ebert & Fabien Labroussaa & Anne Pohlmann & Jacqueline King & Silvio Steiner & Jenna N. Kelly & Jasmine Portmann & Nico Joel Ha, 2021. "SARS-CoV-2 spike D614G change enhances replication and transmission," Nature, Nature, vol. 592(7852), pages 122-127, April.
    • Handle: RePEc:nat:nature:v:592:y:2021:i:7852:d:10.1038_s41586-021-03361-1
    DOI: 10.1038/s41586-021-03361-1
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    Cited by:

    1. Julia R. Port & Claude Kwe Yinda & Jade C. Riopelle & Zachary A. Weishampel & Taylor A. Saturday & Victoria A. Avanzato & Jonathan E. Schulz & Myndi G. Holbrook & Kent Barbian & Rose Perry-Gottschalk , 2023. "Infection- or AZD1222 vaccine-mediated immunity reduces SARS-CoV-2 transmission but increases Omicron competitiveness in hamsters," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    2. X. Tong & R. P. McNamara & M. J. Avendaño & E. F. Serrano & T. García-Salum & C. Pardo-Roa & H. L. Bertera & T. M. Chicz & J. Levican & E. Poblete & E. Salinas & A. Muñoz & A. Riquelme & G. Alter & R., 2023. "Waning and boosting of antibody Fc-effector functions upon SARS-CoV-2 vaccination," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    3. Peter Radvak & Hyung-Joon Kwon & Martina Kosikova & Uriel Ortega-Rodriguez & Ruoxuan Xiang & Je-Nie Phue & Rong-Fong Shen & James Rozzelle & Neeraj Kapoor & Taylor Rabara & Jeff Fairman & Hang Xie, 2021. "SARS-CoV-2 B.1.1.7 (alpha) and B.1.351 (beta) variants induce pathogenic patterns in K18-hACE2 transgenic mice distinct from early strains," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    4. Cassia Wagner & Kathryn E. Kistler & Garrett A. Perchetti & Noah Baker & Lauren A. Frisbie & Laura Marcela Torres & Frank Aragona & Cory Yun & Marlin Figgins & Alexander L. Greninger & Alex Cox & Hann, 2024. "Positive selection underlies repeated knockout of ORF8 in SARS-CoV-2 evolution," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    5. G. Tuba Barut & Nico Joel Halwe & Adriano Taddeo & Jenna N. Kelly & Jacob Schön & Nadine Ebert & Lorenz Ulrich & Christelle Devisme & Silvio Steiner & Bettina Salome Trüeb & Bernd Hoffmann & Inês Bere, 2022. "The spike gene is a major determinant for the SARS-CoV-2 Omicron-BA.1 phenotype," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    6. Louisa L. Y. Chan & Danielle E. Anderson & Hong Sheng Cheng & Fransiskus Xaverius Ivan & Si Chen & Adrian E. Z. Kang & Randy Foo & Akshamal M. Gamage & Pei Yee Tiew & Mariko Siyue Koh & Ken Cheah Hooi, 2022. "The establishment of COPD organoids to study host-pathogen interaction reveals enhanced viral fitness of SARS-CoV-2 in bronchi," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    7. Wenjuan Dong & Jing Wang & Lei Tian & Jianying Zhang & Erik W. Settles & Chao Qin & Daniel R. Steinken-Kollath & Ashley N. Itogawa & Kimberly R. Celona & Jinhee Yi & Mitchell Bryant & Heather Mead & S, 2023. "Factor Xa cleaves SARS-CoV-2 spike protein to block viral entry and infection," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    8. Meriem Bekliz & Kenneth Adea & Pauline Vetter & Christiane S. Eberhardt & Krisztina Hosszu-Fellous & Diem-Lan Vu & Olha Puhach & Manel Essaidi-Laziosi & Sophie Waldvogel-Abramowski & Caroline Stephan , 2022. "Neutralization capacity of antibodies elicited through homologous or heterologous infection or vaccination against SARS-CoV-2 VOCs," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    9. Tamara Kaleta & Lisa Kern & Samuel Leandro Hong & Martin Hölzer & Georg Kochs & Julius Beer & Daniel Schnepf & Martin Schwemmle & Nena Bollen & Philipp Kolb & Magdalena Huber & Svenja Ulferts & Sebast, 2022. "Antibody escape and global spread of SARS-CoV-2 lineage A.27," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    10. Li Wang & Markus H. Kainulainen & Nannan Jiang & Han Di & Gaston Bonenfant & Lisa Mills & Michael Currier & Punya Shrivastava-Ranjan & Brenda M. Calderon & Mili Sheth & Brian R. Mann & Jaber Hossain &, 2022. "Differential neutralization and inhibition of SARS-CoV-2 variants by antibodies elicited by COVID-19 mRNA vaccines," Nature Communications, Nature, vol. 13(1), pages 1-10, December.

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