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The N501Y spike substitution enhances SARS-CoV-2 infection and transmission

Author

Listed:
  • Yang Liu

    (University of Texas Medical Branch
    University of Texas Medical Branch)

  • Jianying Liu

    (University of Texas Medical Branch
    University of Texas Medical Branch
    University of Texas Medical Branch)

  • Kenneth S. Plante

    (University of Texas Medical Branch
    University of Texas Medical Branch
    University of Texas Medical Branch)

  • Jessica A. Plante

    (University of Texas Medical Branch
    University of Texas Medical Branch
    University of Texas Medical Branch)

  • Xuping Xie

    (University of Texas Medical Branch)

  • Xianwen Zhang

    (University of Texas Medical Branch)

  • Zhiqiang Ku

    (The University of Texas Health Science Center at Houston)

  • Zhiqiang An

    (The University of Texas Health Science Center at Houston)

  • Dionna Scharton

    (University of Texas Medical Branch
    University of Texas Medical Branch
    University of Texas Medical Branch)

  • Craig Schindewolf

    (University of Texas Medical Branch
    University of Texas Medical Branch)

  • Steven G. Widen

    (University of Texas Medical Branch)

  • Vineet D. Menachery

    (University of Texas Medical Branch
    University of Texas Medical Branch)

  • Pei-Yong Shi

    (University of Texas Medical Branch
    University of Texas Medical Branch)

  • Scott C. Weaver

    (University of Texas Medical Branch
    University of Texas Medical Branch
    University of Texas Medical Branch)

Abstract

The B.1.1.7 variant (also known as Alpha) of SARS-CoV-2, the cause of the COVID-19 pandemic, emerged in the UK in the summer of 2020. The prevalence of this variant increased rapidly owing to an increase in infection and/or transmission efficiency1. The Alpha variant contains 19 nonsynonymous mutations across its viral genome, including 8 substitutions or deletions in the spike protein that interacts with cellular receptors to mediate infection and tropism. Here, using a reverse genetics approach, we show that of the 8 individual spike protein substitutions, only N501Y resulted in consistent fitness gains for replication in the upper airway in a hamster model as well as in primary human airway epithelial cells. The N501Y substitution recapitulated the enhanced viral transmission phenotype of the eight mutations in the Alpha spike protein, suggesting that it is a major determinant of the increased transmission of the Alpha variant. Mechanistically, the N501Y substitution increased the affinity of the viral spike protein for cellular receptors. As suggested by its convergent evolution in Brazil, South Africa and elsewhere2,3, our results indicate that N501Y substitution is an adaptive spike mutation of major concern.

Suggested Citation

  • Yang Liu & Jianying Liu & Kenneth S. Plante & Jessica A. Plante & Xuping Xie & Xianwen Zhang & Zhiqiang Ku & Zhiqiang An & Dionna Scharton & Craig Schindewolf & Steven G. Widen & Vineet D. Menachery &, 2022. "The N501Y spike substitution enhances SARS-CoV-2 infection and transmission," Nature, Nature, vol. 602(7896), pages 294-299, February.
  • Handle: RePEc:nat:nature:v:602:y:2022:i:7896:d:10.1038_s41586-021-04245-0
    DOI: 10.1038/s41586-021-04245-0
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    Cited by:

    1. Aijing Feng & Sarah Bevins & Jeff Chandler & Thomas J. DeLiberto & Ria Ghai & Kristina Lantz & Julianna Lenoch & Adam Retchless & Susan Shriner & Cynthia Y. Tang & Suxiang Sue Tong & Mia Torchetti & A, 2023. "Transmission of SARS-CoV-2 in free-ranging white-tailed deer in the United States," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Mingxi Li & Yifei Ren & Zhen Qin Aw & Bo Chen & Ziqing Yang & Yuqing Lei & Lin Cheng & Qingtai Liang & Junxian Hong & Yiling Yang & Jing Chen & Yi Hao Wong & Jing Wei & Sisi Shan & Senyan Zhang & Jiwa, 2022. "Broadly neutralizing and protective nanobodies against SARS-CoV-2 Omicron subvariants BA.1, BA.2, and BA.4/5 and diverse sarbecoviruses," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    3. RĂºbens Prince dos Santos Alves & Julia Timis & Robyn Miller & Kristen Valentine & Paolla Beatriz Almeida Pinto & Andrew Gonzalez & Jose Angel Regla-Nava & Erin Maule & Michael N. Nguyen & Norazizah Sh, 2024. "Human coronavirus OC43-elicited CD4+ T cells protect against SARS-CoV-2 in HLA transgenic mice," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    4. Chang Liu & Raksha Das & Aiste Dijokaite-Guraliuc & Daming Zhou & Alexander J. Mentzer & Piyada Supasa & Muneeswaran Selvaraj & Helen M. E. Duyvesteyn & Thomas G. Ritter & Nigel Temperton & Paul Klene, 2024. "Emerging variants develop total escape from potent monoclonal antibodies induced by BA.4/5 infection," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    5. Dillon S. McBride & Sofya K. Garushyants & John Franks & Andrew F. Magee & Steven H. Overend & Devra Huey & Amanda M. Williams & Seth A. Faith & Ahmed Kandeil & Sanja Trifkovic & Lance Miller & Trusha, 2023. "Accelerated evolution of SARS-CoV-2 in free-ranging white-tailed deer," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    6. 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.

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