IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-33632-y.html
   My bibliography  Save this article

The spike gene is a major determinant for the SARS-CoV-2 Omicron-BA.1 phenotype

Author

Listed:
  • G. Tuba Barut

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern)

  • Nico Joel Halwe

    (Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems)

  • Adriano Taddeo

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern)

  • Jenna N. Kelly

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern
    University of Bern
    European Virus Bioinformatics Center)

  • Jacob Schön

    (Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems)

  • Nadine Ebert

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern)

  • Lorenz Ulrich

    (Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems)

  • Christelle Devisme

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern)

  • Silvio Steiner

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern)

  • Bettina Salome Trüeb

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern)

  • Bernd Hoffmann

    (Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems)

  • Inês Berenguer Veiga

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern)

  • Nathan Georges François Leborgne

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern)

  • Etori Aguiar Moreira

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern)

  • Angele Breithaupt

    (Friedrich-Loeffler-Institut, Greifswald-Insel Riems)

  • Claudia Wylezich

    (Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems)

  • Dirk Höper

    (Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems)

  • Kerstin Wernike

    (Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems)

  • Aurélie Godel

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern)

  • Lisa Thomann

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern)

  • Vera Flück

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern)

  • Hanspeter Stalder

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern)

  • Melanie Brügger

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern)

  • Blandina I. Oliveira Esteves

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern)

  • Beatrice Zumkehr

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern)

  • Guillaume Beilleau

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern
    University of Bern)

  • Annika Kratzel

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern)

  • Kimberly Schmied

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern)

  • Sarah Ochsenbein

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern)

  • Reto M. Lang

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern
    University of Bern)

  • Manon Wider

    (University of Bern)

  • Carlos Machahua

    (Bern University Hospital, University of Bern
    University of Bern)

  • Patrick Dorn

    (Bern University Hospital, University of Bern
    Bern University Hospital, University of Bern)

  • Thomas M. Marti

    (Bern University Hospital, University of Bern
    Bern University Hospital, University of Bern)

  • Manuela Funke-Chambour

    (Bern University Hospital, University of Bern
    University of Bern)

  • Andri Rauch

    (University of Bern
    Bern University Hospital, University of Bern)

  • Marek Widera

    (University Hospital Frankfurt, Goethe University)

  • Sandra Ciesek

    (University Hospital Frankfurt, Goethe University)

  • Ronald Dijkman

    (University of Bern
    European Virus Bioinformatics Center
    University of Bern)

  • Donata Hoffmann

    (Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems)

  • Marco P. Alves

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern
    University of Bern)

  • Charaf Benarafa

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern
    University of Bern)

  • Martin Beer

    (Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems
    European Virus Bioinformatics Center)

  • Volker Thiel

    (Institute of Virology and Immunology, Bern and Mittelhäusern
    University of Bern
    University of Bern
    European Virus Bioinformatics Center)

Abstract

Variant of concern (VOC) Omicron-BA.1 has achieved global predominance in early 2022. Therefore, surveillance and comprehensive characterization of Omicron-BA.1 in advanced primary cell culture systems and animal models are urgently needed. Here, we characterize Omicron-BA.1 and recombinant Omicron-BA.1 spike gene mutants in comparison with VOC Delta in well-differentiated primary human nasal and bronchial epithelial cells in vitro, followed by in vivo fitness characterization in hamsters, ferrets and hACE2-expressing mice, and immunized hACE2-mice. We demonstrate a spike-mediated enhancement of early replication of Omicron-BA.1 in nasal epithelial cultures, but limited replication in bronchial epithelial cultures. In hamsters, Delta shows dominance over Omicron-BA.1, and in ferrets Omicron-BA.1 infection is abortive. In hACE2-knock-in mice, Delta and a Delta spike clone also show dominance over Omicron-BA.1 and an Omicron-BA.1 spike clone, respectively. Interestingly, in naïve K18-hACE2 mice, we observe Delta spike-mediated increased replication and pathogenicity and Omicron-BA.1 spike-mediated reduced replication and pathogenicity, suggesting that the spike gene is a major determinant of replication and pathogenicity. Finally, the Omicron-BA.1 spike clone is less well-controlled by mRNA-vaccination in K18-hACE2-mice and becomes more competitive compared to the progenitor and Delta spike clones, suggesting that spike gene-mediated immune evasion is another important factor that led to Omicron-BA.1 dominance.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33632-y
    DOI: 10.1038/s41467-022-33632-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-33632-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-33632-y?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
    ---><---

    References listed on IDEAS

    as
    1. Sandile Cele & Laurelle Jackson & David S. Khoury & Khadija Khan & Thandeka Moyo-Gwete & Houriiyah Tegally & James Emmanuel San & Deborah Cromer & Cathrine Scheepers & Daniel G. Amoako & Farina Karim , 2022. "Omicron extensively but incompletely escapes Pfizer BNT162b2 neutralization," Nature, Nature, vol. 602(7898), pages 654-656, February.
    2. 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.
    3. Tran Thao & Fabien Labroussaa & Nadine Ebert & Philip V’kovski & Hanspeter Stalder & Jasmine Portmann & Jenna Kelly & Silvio Steiner & Melle Holwerda & Annika Kratzel & Mitra Gultom & Kimberly Schmied, 2020. "Rapid reconstruction of SARS-CoV-2 using a synthetic genomics platform," Nature, Nature, vol. 582(7813), pages 561-565, June.
    4. Jessica A. Plante & Yang Liu & Jianying Liu & Hongjie Xia & Bryan A. Johnson & Kumari G. Lokugamage & Xianwen Zhang & Antonio E. Muruato & Jing Zou & Camila R. Fontes-Garfias & Divya Mirchandani & Dio, 2021. "Spike mutation D614G alters SARS-CoV-2 fitness," Nature, Nature, vol. 592(7852), pages 116-121, April.
    5. 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.
    6. Jessica A. Plante & Yang Liu & Jianying Liu & Hongjie Xia & Bryan A. Johnson & Kumari G. Lokugamage & Xianwen Zhang & Antonio E. Muruato & Jing Zou & Camila R. Fontes-Garfias & Divya Mirchandani & Dio, 2021. "Author Correction: Spike mutation D614G alters SARS-CoV-2 fitness," Nature, Nature, vol. 595(7865), pages 1-1, July.
    Full references (including those not matched with items on IDEAS)

    Citations

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


    Cited by:

    1. Markus Hoffmann & Lok-Yin Roy Wong & Prerna Arora & Lu Zhang & Cheila Rocha & Abby Odle & Inga Nehlmeier & Amy Kempf & Anja Richter & Nico Joel Halwe & Jacob Schön & Lorenz Ulrich & Donata Hoffmann & , 2023. "Omicron subvariant BA.5 efficiently infects lung cells," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    2. Taha Y. Taha & Irene P. Chen & Jennifer M. Hayashi & Takako Tabata & Keith Walcott & Gabriella R. Kimmerly & Abdullah M. Syed & Alison Ciling & Rahul K. Suryawanshi & Hannah S. Martin & Bryan H. Bach , 2023. "Rapid assembly of SARS-CoV-2 genomes reveals attenuation of the Omicron BA.1 variant through NSP6," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    3. Anthony Petkidis & Vardan Andriasyan & Luca Murer & Romain Volle & Urs F. Greber, 2024. "A versatile automated pipeline for quantifying virus infectivity by label-free light microscopy and artificial intelligence," Nature Communications, Nature, vol. 15(1), pages 1-11, December.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. 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.
    2. 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.
    3. Yang Liu & Xianwen Zhang & Jianying Liu & Hongjie Xia & Jing Zou & Antonio E. Muruato & Sivakumar Periasamy & Chaitanya Kurhade & Jessica A. Plante & Nathen E. Bopp & Birte Kalveram & Alexander Bukrey, 2022. "A live-attenuated SARS-CoV-2 vaccine candidate with accessory protein deletions," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    4. 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.
    5. Chaitanya Kurhade & Jing Zou & Hongjie Xia & Hui Cai & Qi Yang & Mark Cutler & David Cooper & Alexander Muik & Kathrin U. Jansen & Xuping Xie & Kena A. Swanson & Pei‑Yong Shi, 2022. "Neutralization of Omicron BA.1, BA.2, and BA.3 SARS-CoV-2 by 3 doses of BNT162b2 vaccine," Nature Communications, Nature, vol. 13(1), pages 1-4, December.
    6. 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.
    7. Federico Armando & Georg Beythien & Franziska K. Kaiser & Lisa Allnoch & Laura Heydemann & Malgorzata Rosiak & Svenja Becker & Mariana Gonzalez-Hernandez & Mart M. Lamers & Bart L. Haagmans & Kate Gui, 2022. "SARS-CoV-2 Omicron variant causes mild pathology in the upper and lower respiratory tract of hamsters," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    8. Asolina Braun & Louise C. Rowntree & Ziyi Huang & Kirti Pandey & Nikolas Thuesen & Chen Li & Jan Petersen & Dene R. Littler & Shabana Raji & Thi H. O. Nguyen & Emma Jappe Lange & Gry Persson & Michael, 2024. "Mapping the immunopeptidome of seven SARS-CoV-2 antigens across common HLA haplotypes," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    9. Egon A. Ozer & Lacy M. Simons & Olubusuyi M. Adewumi & Adeola A. Fowotade & Ewean C. Omoruyi & Johnson A. Adeniji & Oluseyi A. Olayinka & Taylor J. Dean & Janet Zayas & Pavan P. Bhimalli & Michelle K., 2022. "Multiple expansions of globally uncommon SARS-CoV-2 lineages in Nigeria," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    10. Ren Ren & Shenglin Cai & Xiaona Fang & Xiaoyi Wang & Zheng Zhang & Micol Damiani & Charlotte Hudlerova & Annachiara Rosa & Joshua Hope & Nicola J. Cook & Peter Gorelkin & Alexander Erofeev & Pavel Nov, 2023. "Multiplexed detection of viral antigen and RNA using nanopore sensing and encoded molecular probes," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    11. Pauline Maisonnasse & Yoann Aldon & Aurélien Marc & Romain Marlin & Nathalie Dereuddre-Bosquet & Natalia A. Kuzmina & Alec W. Freyn & Jonne L. Snitselaar & Antonio Gonçalves & Tom G. Caniels & Judith , 2021. "COVA1-18 neutralizing antibody protects against SARS-CoV-2 in three preclinical models," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    12. Taha Y. Taha & Irene P. Chen & Jennifer M. Hayashi & Takako Tabata & Keith Walcott & Gabriella R. Kimmerly & Abdullah M. Syed & Alison Ciling & Rahul K. Suryawanshi & Hannah S. Martin & Bryan H. Bach , 2023. "Rapid assembly of SARS-CoV-2 genomes reveals attenuation of the Omicron BA.1 variant through NSP6," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    13. Hassen Kared & Asia-Sophia Wolf & Amin Alirezaylavasani & Anthony Ravussin & Guri Solum & Trung The Tran & Fridtjof Lund-Johansen & John Torgils Vaage & Lise Sofie Nissen-Meyer & Unni C. Nygaard & Ola, 2022. "Immune responses in Omicron SARS-CoV-2 breakthrough infection in vaccinated adults," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    14. 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.
    15. Suman Das & Janmejay Singh & Heena Shaman & Balwant Singh & Anbalagan Anantharaj & Patil Sharanabasava & Rajesh Pandey & Rakesh Lodha & Anil Kumar Pandey & Guruprasad R. Medigeshi, 2022. "Pre-existing antibody levels negatively correlate with antibody titers after a single dose of BBV152 vaccination," Nature Communications, Nature, vol. 13(1), pages 1-7, December.
    16. Seoryeong Park & Jaewon Choi & Yonghee Lee & Jinsung Noh & Namphil Kim & JinAh Lee & Geummi Cho & Sujeong Kim & Duck Kyun Yoo & Chang Kyung Kang & Pyoeng Gyun Choe & Nam Joong Kim & Wan Beom Park & Se, 2024. "An ancestral SARS-CoV-2 vaccine induces anti-Omicron variants antibodies by hypermutation," Nature Communications, Nature, vol. 15(1), pages 1-9, December.
    17. Akshay J. Maheshwari & Jonathan Calles & Sean K. Waterton & Drew Endy, 2023. "Engineering tRNA abundances for synthetic cellular systems," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    18. Bo Qin & Ziheng Li & Kaiming Tang & Tongyun Wang & Yubin Xie & Sylvain Aumonier & Meitian Wang & Shuofeng Yuan & Sheng Cui, 2023. "Identification of the SARS-unique domain of SARS-CoV-2 as an antiviral target," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    19. Raffaele Palladino & Michelangelo Mercogliano & Claudio Fiorilla & Alessandro Frangiosa & Sabrina Iodice & Stefano Sanduzzi Zamparelli & Emma Montella & Maria Triassi & Alessandro Sanduzzi Zamparelli, 2022. "Association between COVID-19 and Sick Leave for Healthcare Workers in a Large Academic Hospital in Southern Italy: An Observational Study," IJERPH, MDPI, vol. 19(15), pages 1-8, August.
    20. Oskar Staufer & Gösta Gantner & Ilia Platzman & Klaus Tanner & Imre Berger & Joachim P. Spatz, 2022. "Bottom-up assembly of viral replication cycles," Nature Communications, Nature, vol. 13(1), pages 1-10, 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:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33632-y. 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.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with 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.