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Characterization of SARS-CoV-2 Spike mutations important for infection of mice and escape from human immune sera

Author

Listed:
  • Raveen Rathnasinghe

    (Icahn School of Medicine at Mount Sinai New York
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai New York
    Seqirus)

  • Sonia Jangra

    (Icahn School of Medicine at Mount Sinai New York
    Icahn School of Medicine at Mount Sinai New York)

  • Chengjin Ye

    (Texas Biomedical Research Institute)

  • Anastasija Cupic

    (Icahn School of Medicine at Mount Sinai New York
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai New York)

  • Gagandeep Singh

    (Icahn School of Medicine at Mount Sinai New York
    Icahn School of Medicine at Mount Sinai New York)

  • Carles Martínez-Romero

    (Icahn School of Medicine at Mount Sinai New York
    Icahn School of Medicine at Mount Sinai New York)

  • Lubbertus C. F. Mulder

    (Icahn School of Medicine at Mount Sinai New York
    Icahn School of Medicine at Mount Sinai New York)

  • Thomas Kehrer

    (Icahn School of Medicine at Mount Sinai New York
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai New York)

  • Soner Yildiz

    (Icahn School of Medicine at Mount Sinai New York
    Icahn School of Medicine at Mount Sinai New York)

  • Angela Choi

    (Icahn School of Medicine at Mount Sinai New York
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai New York
    Moderna Therapeutics)

  • Stephen T. Yeung

    (Weill Cornell Medicine, New York)

  • Ignacio Mena

    (Icahn School of Medicine at Mount Sinai New York
    Icahn School of Medicine at Mount Sinai New York)

  • Virginia Gillespie

    (Icahn School of Medicine at Mount Sinai New York)

  • Jana Vrieze

    (Ghent University)

  • Sadaf Aslam

    (Icahn School of Medicine at Mount Sinai New York
    Icahn School of Medicine at Mount Sinai New York)

  • Daniel Stadlbauer

    (Icahn School of Medicine at Mount Sinai New York
    Moderna Therapeutics)

  • David A. Meekins

    (Kansas State University)

  • Chester D. McDowell

    (Kansas State University)

  • Velmurugan Balaraman

    (Kansas State University)

  • Michael J. Corley

    (Weill Cornell Medicine, New York)

  • Juergen A. Richt

    (Kansas State University)

  • Bruno G. Geest

    (Ghent University)

  • Lisa Miorin

    (Icahn School of Medicine at Mount Sinai New York
    Icahn School of Medicine at Mount Sinai New York)

  • Florian Krammer

    (Icahn School of Medicine at Mount Sinai New York)

  • Luis Martinez-Sobrido

    (Texas Biomedical Research Institute)

  • Viviana Simon

    (Icahn School of Medicine at Mount Sinai New York
    Icahn School of Medicine at Mount Sinai New York
    Icahn School of Medicine at Mount Sinai New York)

  • Adolfo García-Sastre

    (Icahn School of Medicine at Mount Sinai New York
    Icahn School of Medicine at Mount Sinai New York
    Icahn School of Medicine at Mount Sinai New York
    Icahn School of Medicine at Mount Sinai New York)

  • Michael Schotsaert

    (Icahn School of Medicine at Mount Sinai New York
    Icahn School of Medicine at Mount Sinai New York)

Abstract

Due to differences in human and murine angiotensin converting enzyme 2 (ACE-2) receptor, initially available SARS-CoV-2 isolates could not infect mice. Here we show that serial passaging of USA-WA1/2020 strain in mouse lungs results in “mouse-adapted” SARS-CoV-2 (MA-SARS-CoV-2) with mutations in S, M, and N genes, and a twelve-nucleotide insertion in the S gene. MA-SARS-CoV-2 infection causes mild disease, with more pronounced morbidity depending on genetic background and in aged and obese mice. Two mutations in the S gene associated with mouse adaptation (N501Y, H655Y) are present in SARS-CoV-2 variants of concern (VoCs). N501Y in the receptor binding domain of viruses of the B.1.1.7, B.1.351, P.1 and B.1.1.529 lineages (Alpha, Beta, Gamma and Omicron variants) is associated with high transmissibility and allows VoCs to infect wild type mice. We further show that S protein mutations of MA-SARS-CoV-2 do not affect neutralization efficiency by human convalescent and post vaccination sera.

Suggested Citation

  • Raveen Rathnasinghe & Sonia Jangra & Chengjin Ye & Anastasija Cupic & Gagandeep Singh & Carles Martínez-Romero & Lubbertus C. F. Mulder & Thomas Kehrer & Soner Yildiz & Angela Choi & Stephen T. Yeung , 2022. "Characterization of SARS-CoV-2 Spike mutations important for infection of mice and escape from human immune sera," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30763-0
    DOI: 10.1038/s41467-022-30763-0
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    References listed on IDEAS

    as
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