Characterization of SARS-CoV-2 Spike mutations important for infection of mice and escape from human immune sera.
Raveen RathnasingheSonia JangraChengjin YeAnastasija CupicGagandeep SinghCarles Martínez-RomeroLubbertus C F MulderThomas KehrerSoner YildizAngela ChoiStephen T YeungIgnacio MenaVirginia GillespieJana De VriezeSadaf AslamDaniel StadlbauerDavid A MeekinsChester D McDowellVelmurugan BalaramanMichael J CorleyJuergen A RichtBruno G De GeestLisa Miorinnull nullFlorian KrammerLuis Martinez-SobridoViviana SimonAdolfo García-SastreMichael SchotsaertPublished in: Nature communications (2022)
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.
Keyphrases
- sars cov
- respiratory syndrome coronavirus
- wild type
- endothelial cells
- copy number
- angiotensin converting enzyme
- genome wide
- high fat diet induced
- angiotensin ii
- induced pluripotent stem cells
- pluripotent stem cells
- binding protein
- type diabetes
- dna methylation
- metabolic syndrome
- gene expression
- coronavirus disease
- insulin resistance
- skeletal muscle
- dna binding