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

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, Ignacio Mena, Virginia Gillespie, Jana Vrieze, Sadaf Aslam, Daniel Stadlbauer, David A. Meekins, Chester D. McDowell, Velmurugan Balaraman, Michael J. Corley, Juergen A. Richt, Bruno G. Geest, Lisa Miorin, Florian Krammer, Luis Martinez-Sobrido, Viviana Simon, Adolfo García-Sastre () and Michael Schotsaert ()
Additional contact information
Raveen Rathnasinghe: Icahn School of Medicine at Mount Sinai New York
Sonia Jangra: 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
Gagandeep Singh: Icahn School of Medicine at Mount Sinai New York
Carles Martínez-Romero: Icahn School of Medicine at Mount Sinai New York
Lubbertus C. F. Mulder: Icahn School of Medicine at Mount Sinai New York
Thomas Kehrer: Icahn School of Medicine at Mount Sinai New York
Soner Yildiz: Icahn School of Medicine at Mount Sinai New York
Angela Choi: Icahn School of Medicine at Mount Sinai New York
Stephen T. Yeung: Weill Cornell Medicine, New York
Ignacio Mena: 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
Daniel Stadlbauer: Icahn School of Medicine at Mount Sinai New York
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
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
Adolfo García-Sastre: Icahn School of Medicine at Mount Sinai New York
Michael Schotsaert: Icahn School of Medicine at Mount Sinai New York

Nature Communications, 2022, vol. 13, issue 1, 1-14

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-30763-0

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