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

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.

SUBMITTER: Rathnasinghe R

PROVIDER: S-EPMC9261898 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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

Rathnasinghe Raveen R Jangra Sonia S Ye Chengjin C Cupic Anastasija A Singh Gagandeep G Martínez-Romero Carles C Mulder Lubbertus C F LCF Kehrer Thomas T Yildiz Soner S Choi Angela A Yeung Stephen T ST Mena Ignacio I Gillespie Virginia V De Vrieze Jana J Aslam Sadaf S Stadlbauer Daniel D Meekins David A DA McDowell Chester D CD Balaraman Velmurugan V Corley Michael J MJ Richt Juergen A JA De Geest Bruno G BG Miorin Lisa L Krammer Florian F Martinez-Sobrido Luis L Simon Viviana V García-Sastre Adolfo A Schotsaert Michael M

Nature communications 20220707 1

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. ...[more]

PMID: 35798721

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Dataset Information

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

Publications

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

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