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The SARS-CoV-2 Y453F mink variant displays a pronounced increase in ACE-2 affinity but does not challenge antibody neutralization.
J Biol Chem. 2021 Jan-Jun; 296:100536.JB

Abstract

Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 from humans to animals has been reported for many domesticated species, including farmed minks. The identification of novel spike gene mutations appearing in minks has raised major concerns about potential immune evasion and challenges for the global vaccine strategy. One genetic variant, known as "cluster five," arose among farmed minks in Denmark and resulted in a complete shutdown of the world's largest mink production. However, the functional properties of this new variant are not established. Here we present functional data on the cluster-five variant, which contains a mutation resulting in a Y453F residue change in the receptor-binding domain (RBD) of the spike protein. Using an ELISA-based angiotensin-converting enzyme-2/RBD inhibition assay, we show that the Y453F variant does not decrease established humoral immunity from previously infected individuals or affect the neutralizing antibody response in a vaccine mouse model based on the original Wuhan strain RBD or spike as antigens. However, biolayer interferometry analysis demonstrates that it binds the human angiotensin-converting enzyme-2 receptor with a 4-fold higher affinity than the original strain, suggesting an enhanced transmission capacity and a possible challenge for viral control. These results also indicate that the rise in the frequency of the cluster-five variant in mink farms might be a result of the fitness advantage conferred by the receptor adaptation rather than evading immune responses.

Authors+Show Affiliations

Laboratory of Molecular Medicine, Department of Clinical Immunology, University Hospital of Copenhagen, Copenhagen, Denmark.Laboratory of Molecular Medicine, Department of Clinical Immunology, University Hospital of Copenhagen, Copenhagen, Denmark; Institute of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.Novo Nordisk A/S, Måløv, Denmark.Novo Nordisk A/S, Måløv, Denmark.Novo Nordisk A/S, Måløv, Denmark.Laboratory of Molecular Medicine, Department of Clinical Immunology, University Hospital of Copenhagen, Copenhagen, Denmark.Laboratory of Molecular Medicine, Department of Clinical Immunology, University Hospital of Copenhagen, Copenhagen, Denmark; Institute of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark. Electronic address: moskjoedt@sund.ku.dk.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33716040

Citation

Bayarri-Olmos, Rafael, et al. "The SARS-CoV-2 Y453F Mink Variant Displays a Pronounced Increase in ACE-2 Affinity but Does Not Challenge Antibody Neutralization." The Journal of Biological Chemistry, vol. 296, 2021, p. 100536.
Bayarri-Olmos R, Rosbjerg A, Johnsen LB, et al. The SARS-CoV-2 Y453F mink variant displays a pronounced increase in ACE-2 affinity but does not challenge antibody neutralization. J Biol Chem. 2021;296:100536.
Bayarri-Olmos, R., Rosbjerg, A., Johnsen, L. B., Helgstrand, C., Bak-Thomsen, T., Garred, P., & Skjoedt, M. O. (2021). The SARS-CoV-2 Y453F mink variant displays a pronounced increase in ACE-2 affinity but does not challenge antibody neutralization. The Journal of Biological Chemistry, 296, 100536. https://doi.org/10.1016/j.jbc.2021.100536
Bayarri-Olmos R, et al. The SARS-CoV-2 Y453F Mink Variant Displays a Pronounced Increase in ACE-2 Affinity but Does Not Challenge Antibody Neutralization. J Biol Chem. 2021 Jan-Jun;296:100536. PubMed PMID: 33716040.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The SARS-CoV-2 Y453F mink variant displays a pronounced increase in ACE-2 affinity but does not challenge antibody neutralization. AU - Bayarri-Olmos,Rafael, AU - Rosbjerg,Anne, AU - Johnsen,Laust Bruun, AU - Helgstrand,Charlotte, AU - Bak-Thomsen,Theresa, AU - Garred,Peter, AU - Skjoedt,Mikkel-Ole, Y1 - 2021/03/11/ PY - 2021/01/28/received PY - 2021/03/02/revised PY - 2021/03/09/accepted PY - 2021/3/16/pubmed PY - 2021/7/14/medline PY - 2021/3/15/entrez KW - ACE-2 KW - RBD KW - RNA virus KW - SARS-CoV-2 KW - Virology KW - antibodies KW - immunology KW - mutant KW - receptor interaction KW - receptor structure–function SP - 100536 EP - 100536 JF - The Journal of biological chemistry JO - J Biol Chem VL - 296 N2 - Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 from humans to animals has been reported for many domesticated species, including farmed minks. The identification of novel spike gene mutations appearing in minks has raised major concerns about potential immune evasion and challenges for the global vaccine strategy. One genetic variant, known as "cluster five," arose among farmed minks in Denmark and resulted in a complete shutdown of the world's largest mink production. However, the functional properties of this new variant are not established. Here we present functional data on the cluster-five variant, which contains a mutation resulting in a Y453F residue change in the receptor-binding domain (RBD) of the spike protein. Using an ELISA-based angiotensin-converting enzyme-2/RBD inhibition assay, we show that the Y453F variant does not decrease established humoral immunity from previously infected individuals or affect the neutralizing antibody response in a vaccine mouse model based on the original Wuhan strain RBD or spike as antigens. However, biolayer interferometry analysis demonstrates that it binds the human angiotensin-converting enzyme-2 receptor with a 4-fold higher affinity than the original strain, suggesting an enhanced transmission capacity and a possible challenge for viral control. These results also indicate that the rise in the frequency of the cluster-five variant in mink farms might be a result of the fitness advantage conferred by the receptor adaptation rather than evading immune responses. SN - 1083-351X UR - https://www.unboundmedicine.com/medline/citation/33716040/The_SARS_CoV_2_Y453F_mink_variant_displays_a_pronounced_increase_in_ACE_2_affinity_but_does_not_challenge_antibody_neutralization_ DB - PRIME DP - Unbound Medicine ER -