Recurrent emergence of SARS-CoV-2 spike deletion H69/V70 and its role in the variant of concern lineage B.1.1.7

Meng, B. et al. (2021) Recurrent emergence of SARS-CoV-2 spike deletion H69/V70 and its role in the variant of concern lineage B.1.1.7. Cell Reports, 35(13), 109292. (doi: 10.1016/j.celrep.2021.109292) (PMID:34166617) (PMCID:PMC8185188)

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We report SARS-CoV-2 spike ΔH69/V70 in multiple independent lineages, often occurring after acquisition of the receptor binding motif replacements such as N439K and Y453F known to increase binding affinity to the ACE2 receptor and confer antibody escape. In vitro, we show that whilst ΔH69/V70 itself is not an antibody evasion mechanism, it increases infectivity associated with enhanced incorporation of cleaved spike into virions. ΔH69/V70 is able to partially rescue infectivity of S proteins that have acquired N439K and Y453F escape mutations by increased spike incorporation. In addition, replacement of H69 and V70 residues in B.1.1.7 spike (where ΔH69/V70 naturally occurs) impairs spike incorporation and entry efficiency of B.1.1.7 spike pseudotyped virus. B.1.1.7 spike mediates faster kinetics of cell-cell fusion than wild type Wuhan-1 D614G, dependent on ΔH69/V70. Therefore, as ΔH69/V70 compensates for immune escape mutations that impair infectivity, continued surveillance for deletions with functional effects is warranted.

Item Type:Articles
Keywords:SARS-CoV-2, COVID-19, antibody escape, neutralising antibodies, infectivity, spike mutation, evasion, resistance, fitness, deletion.
Glasgow Author(s) Enlighten ID:Robertson, Professor David and Harvey, Dr William and Lytras, Spyros
Authors: Meng, B., Kemp, S. A., Papa, G., Datir, R., Ferreira, I. A., Marelli, S., Harvey, W. T., Lytras, S., Mohamed, A., Gallo, G., Thakur, N., Collier, D. A., Mlcochova, P., Duncan, L. M., Carabelli, A. M., Kenyon, J. C., Lever, A. M., De Marco, A., Saliba, C., Culap, K., Cameroni, E., Matheson, N. J., Piccoli, L., Corti, D., James, L. C., Robertson, D. L., Bailey, D., and Gupta, R. K.
College/School:College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Cell Reports
Publisher:Elsevier (Cell Press)
ISSN (Online):2211-1247
Published Online:08 June 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Cell Reports 35(13): 109292
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
Viral Genomics and BioinformaticsAndrew DavisonMedical Research Council (MRC)MC_UU_12014/12III-MRC-GU Centre for Virus Research