Imperial College London
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ProfessorWendyBarclay

Faculty of Medicine, Department of Infectious Disease

Action Medical Research Chair Virology. Head of Department
 
 
 
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Contact

 

+44 (0)20 7594 5035w.barclay

 
 
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Location

 

416Medical SchoolSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Peacock:2022:10.1101/2021.12.31.474653,
author = {Peacock, TP and Brown, JC and Zhou, J and Thakur, N and Sukhova, K and Newman, J and Kugathasan, R and Yan, AWC and Furnon, W and De, Lorenzo G and Cowton, VM and Reuss, D and Moshe, M and Quantrill, JL and Platt, OK and Kaforou, M and Patel, AH and Palmarini, M and Bailey, D and Barclay, WS},
doi = {10.1101/2021.12.31.474653},
title = {The altered entry pathway and antigenic distance of the SARS-CoV-2 Omicron variant map to separate domains of spike protein},
url = {http://dx.doi.org/10.1101/2021.12.31.474653},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - <jats:title>Abstract</jats:title><jats:p>The SARS-CoV-2 Omicron/BA.1 lineage emerged in late 2021 and rapidly displaced the Delta variant before being overtaken itself globally by, the Omicron/BA.2 lineage in early 2022. Here, we describe how Omicron BA.1 and BA.2 show a lower severity phenotype in a hamster model of pathogenicity which maps specifically to the spike gene. We further show that Omicron is attenuated in a lung cell line but replicates more rapidly, albeit to lower peak titres, in human primary nasal cells. This replication phenotype also maps to the spike gene. Omicron spike (including the emerging Omicron lineage BA.4) shows attenuated fusogenicity and a preference for cell entry via the endosomal route. We map the altered Omicron spike entry route and partially map the lower fusogenicity to the S2 domain, particularly the substitution N969K. Finally, we show that pseudovirus with Omicron spike, engineered in the S2 domain to confer a more Delta-like cell entry route retains the antigenic properties of Omicron. This shows a distinct separation between the genetic determinants of these two key Omicron phenotypes, raising the concerning possibility that future variants with large antigenic distance from currently circulating and vaccine strains will not necessarily display the lower intrinsic severity seen during Omicron infection.</jats:p>
AU  - Peacock,TP
AU  - Brown,JC
AU  - Zhou,J
AU  - Thakur,N
AU  - Sukhova,K
AU  - Newman,J
AU  - Kugathasan,R
AU  - Yan,AWC
AU  - Furnon,W
AU  - De,Lorenzo G
AU  - Cowton,VM
AU  - Reuss,D
AU  - Moshe,M
AU  - Quantrill,JL
AU  - Platt,OK
AU  - Kaforou,M
AU  - Patel,AH
AU  - Palmarini,M
AU  - Bailey,D
AU  - Barclay,WS
DO  - 10.1101/2021.12.31.474653
PY  - 2022///
TI  - The altered entry pathway and antigenic distance of the SARS-CoV-2 Omicron variant map to separate domains of spike protein
UR  - http://dx.doi.org/10.1101/2021.12.31.474653
ER  -
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