The alpha/B.1.1.7 SARS-CoV-2 variant exhibits significantly higher affinity for ACE-2 and requires lower inoculation doses to cause disease in K18-hACE2 mice
The alpha/B.1.1.7 SARS-CoV-2 lineage emerged in autumn 2020 in the United Kingdom and transmitted rapidly until winter 2021 when it was responsible for most new COVID-19 cases in many European countries. The incidence domination was likely due to a fitness advantage that could be driven by the recep...
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eLife Sciences Publications Ltd
2021
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oai:doaj.org-article:0dacfd22c5c844a6adf835fea181b8962021-12-01T14:44:38ZThe alpha/B.1.1.7 SARS-CoV-2 variant exhibits significantly higher affinity for ACE-2 and requires lower inoculation doses to cause disease in K18-hACE2 mice10.7554/eLife.700022050-084Xe70002https://doaj.org/article/0dacfd22c5c844a6adf835fea181b8962021-11-01T00:00:00Zhttps://elifesciences.org/articles/70002https://doaj.org/toc/2050-084XThe alpha/B.1.1.7 SARS-CoV-2 lineage emerged in autumn 2020 in the United Kingdom and transmitted rapidly until winter 2021 when it was responsible for most new COVID-19 cases in many European countries. The incidence domination was likely due to a fitness advantage that could be driven by the receptor-binding domain (RBD) residue change (N501Y), which also emerged independently in other variants of concern such as the beta/B.1.351 and gamma/P.1 strains. Here, we present a functional characterization of the alpha/B.1.1.7 variant and show an eightfold affinity increase towards human angiotensin-converting enzyme-2 (ACE-2). In accordance with this, transgenic hACE2 mice showed a faster disease progression and severity after infection with a low dose of B.1.1.7, compared to an early 2020 SARS-CoV-2 isolate. When challenged with sera from convalescent individuals or anti-RBD monoclonal antibodies, the N501Y variant showed a minor, but significant elevated evasion potential of ACE-2/RBD antibody neutralization. The data suggest that the single asparagine to tyrosine substitution remarkable rise in affinity may be responsible for the higher transmission rate and severity of the B.1.1.7 variant.Rafael Bayarri-OlmosLaust Bruun JohnsenManja IdornLine S ReinertAnne RosbjergSøren VangCecilie Bo HansenCharlotte HelgstrandJais Rose BjelkeTheresa Bak-ThomsenSøren R PaludanPeter GarredMikkel-Ole SkjoedteLife Sciences Publications LtdarticleimmunologyepidemiologySARS-CoV-2mouse modelhumanMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021) |
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DOAJ |
| collection |
DOAJ |
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EN |
| topic |
immunology epidemiology SARS-CoV-2 mouse model human Medicine R Science Q Biology (General) QH301-705.5 |
| spellingShingle |
immunology epidemiology SARS-CoV-2 mouse model human Medicine R Science Q Biology (General) QH301-705.5 Rafael Bayarri-Olmos Laust Bruun Johnsen Manja Idorn Line S Reinert Anne Rosbjerg Søren Vang Cecilie Bo Hansen Charlotte Helgstrand Jais Rose Bjelke Theresa Bak-Thomsen Søren R Paludan Peter Garred Mikkel-Ole Skjoedt The alpha/B.1.1.7 SARS-CoV-2 variant exhibits significantly higher affinity for ACE-2 and requires lower inoculation doses to cause disease in K18-hACE2 mice |
| description |
The alpha/B.1.1.7 SARS-CoV-2 lineage emerged in autumn 2020 in the United Kingdom and transmitted rapidly until winter 2021 when it was responsible for most new COVID-19 cases in many European countries. The incidence domination was likely due to a fitness advantage that could be driven by the receptor-binding domain (RBD) residue change (N501Y), which also emerged independently in other variants of concern such as the beta/B.1.351 and gamma/P.1 strains. Here, we present a functional characterization of the alpha/B.1.1.7 variant and show an eightfold affinity increase towards human angiotensin-converting enzyme-2 (ACE-2). In accordance with this, transgenic hACE2 mice showed a faster disease progression and severity after infection with a low dose of B.1.1.7, compared to an early 2020 SARS-CoV-2 isolate. When challenged with sera from convalescent individuals or anti-RBD monoclonal antibodies, the N501Y variant showed a minor, but significant elevated evasion potential of ACE-2/RBD antibody neutralization. The data suggest that the single asparagine to tyrosine substitution remarkable rise in affinity may be responsible for the higher transmission rate and severity of the B.1.1.7 variant. |
| format |
article |
| author |
Rafael Bayarri-Olmos Laust Bruun Johnsen Manja Idorn Line S Reinert Anne Rosbjerg Søren Vang Cecilie Bo Hansen Charlotte Helgstrand Jais Rose Bjelke Theresa Bak-Thomsen Søren R Paludan Peter Garred Mikkel-Ole Skjoedt |
| author_facet |
Rafael Bayarri-Olmos Laust Bruun Johnsen Manja Idorn Line S Reinert Anne Rosbjerg Søren Vang Cecilie Bo Hansen Charlotte Helgstrand Jais Rose Bjelke Theresa Bak-Thomsen Søren R Paludan Peter Garred Mikkel-Ole Skjoedt |
| author_sort |
Rafael Bayarri-Olmos |
| title |
The alpha/B.1.1.7 SARS-CoV-2 variant exhibits significantly higher affinity for ACE-2 and requires lower inoculation doses to cause disease in K18-hACE2 mice |
| title_short |
The alpha/B.1.1.7 SARS-CoV-2 variant exhibits significantly higher affinity for ACE-2 and requires lower inoculation doses to cause disease in K18-hACE2 mice |
| title_full |
The alpha/B.1.1.7 SARS-CoV-2 variant exhibits significantly higher affinity for ACE-2 and requires lower inoculation doses to cause disease in K18-hACE2 mice |
| title_fullStr |
The alpha/B.1.1.7 SARS-CoV-2 variant exhibits significantly higher affinity for ACE-2 and requires lower inoculation doses to cause disease in K18-hACE2 mice |
| title_full_unstemmed |
The alpha/B.1.1.7 SARS-CoV-2 variant exhibits significantly higher affinity for ACE-2 and requires lower inoculation doses to cause disease in K18-hACE2 mice |
| title_sort |
alpha/b.1.1.7 sars-cov-2 variant exhibits significantly higher affinity for ace-2 and requires lower inoculation doses to cause disease in k18-hace2 mice |
| publisher |
eLife Sciences Publications Ltd |
| publishDate |
2021 |
| url |
https://doaj.org/article/0dacfd22c5c844a6adf835fea181b896 |
| work_keys_str_mv |
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