IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v592y2021i7852d10.1038_s41586-021-03361-1.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41586-021-03361-1
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/s41586-021-03361-1?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    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. 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.
    3. 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.
    4. 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.
    5. 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.
    6. 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.
    7. 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.
    8. 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.
    9. 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.
    10. 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.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:592:y:2021:i:7852:d:10.1038_s41586-021-03361-1. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.