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

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

We report severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike ΔH69/V70 in multiple independent lineages, often occurring after acquisition of 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, although 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 spike proteins that have acquired N439K and Y453F escape mutations by increased spike incorporation. In addition, replacement of the H69 and V70 residues in the Alpha variant B.1.1.7 spike (where ΔH69/V70 occurs naturally) impairs spike incorporation and entry efficiency of the B.1.1.7 spike pseudotyped virus. Alpha variant 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.

Animals, Antibodies, Neutralizing/immunology, Antibodies, Viral/immunology, COVID-19/immunology, Cell Line, Chlorocebus aethiops, HEK293 Cells, Humans, Immune Evasion, Mutation, Pandemics, Phylogeny, Protein Binding, Recurrence, SARS-CoV-2/genetics, Spike Glycoprotein, Coronavirus/genetics, Vero Cells
2211-1247
109292
Meng, Bo
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Kemp, Steven A.
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Papa, Guido
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Datir, Rawlings
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Marelli, Sara
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Lytras, Spyros
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Mohamed, Ahmed
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Gallo, Giulia
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Thakur, Nazia
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Collier, Dami A.
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Mlcochova, Petra
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Robson, Samuel C.
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Martinez Nunez, Rocio T.
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Saeed, Kordo
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Williams, Thomas
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Moore, Christopher
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Paul, Hannah
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Williams, Charlotte A.
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Taylor, Sarah
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Jones, Sophie
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Jones, Rachel
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Patel, Minal
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Smith, Louise
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Partridge, David G.
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Harrison, James W.
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Williams, David
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Pearson, Clare
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Gregory, Richard
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Baker, David J.
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Tucker, Rachel M.
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Brown, Rebecca
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Cook, Elizabeth
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Holmes, Sarah
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Jones, Matthew
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Robinson, David
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Walker, Matthew
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Saeed, Kordo
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The COVID-19 Genomics UK (COG-UK) Consortium
Meng, Bo
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Kemp, Steven A.
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Papa, Guido
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Datir, Rawlings
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Ferreira, Isabella A.T.M.
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Marelli, Sara
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Harvey, William T.
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Lytras, Spyros
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Mohamed, Ahmed
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Gallo, Giulia
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Thakur, Nazia
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Collier, Dami A.
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Mlcochova, Petra
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Robson, Samuel C.
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Martinez Nunez, Rocio T.
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Saeed, Kordo
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Prieto, Jacqui A.
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Shepherd, James G.
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Parker, Matthew D.
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Simpson, David A.
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Jones, Christopher R.
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Holmes, Christopher
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Williams, Thomas
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Moore, Christopher
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Paul, Hannah
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Williams, Charlotte A.
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Taylor, Sarah
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Jones, Sophie
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Baxter, Laura
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Jones, Rachel
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Young, Jamie
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Patel, Minal
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Smith, Louise
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Partridge, David G.
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Harrison, James W.
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Williams, David
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Pearson, Clare
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Gregory, Richard
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Baker, David J.
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Tucker, Rachel M.
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Brown, Rebecca
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Cook, Elizabeth
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Holmes, Sarah
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Jackson, Adam
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Jones, Matthew
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Robinson, David
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Rose, Mark
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Smith, James
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Saeed, Kordo
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Saeed, Kordo , The COVID-19 Genomics UK (COG-UK) Consortium (2021) Recurrent emergence of SARS-CoV-2 spike deletion H69/V70 and its role in the Alpha variant B.1.1.7. Cell Reports, 35 (13), 109292, [109292]. (doi:10.1016/j.celrep.2021.109292).

Record type: Article

Abstract

We report severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike ΔH69/V70 in multiple independent lineages, often occurring after acquisition of 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, although 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 spike proteins that have acquired N439K and Y453F escape mutations by increased spike incorporation. In addition, replacement of the H69 and V70 residues in the Alpha variant B.1.1.7 spike (where ΔH69/V70 occurs naturally) impairs spike incorporation and entry efficiency of the B.1.1.7 spike pseudotyped virus. Alpha variant 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.

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More information

Published date: 29 June 2021
Keywords: Animals, Antibodies, Neutralizing/immunology, Antibodies, Viral/immunology, COVID-19/immunology, Cell Line, Chlorocebus aethiops, HEK293 Cells, Humans, Immune Evasion, Mutation, Pandemics, Phylogeny, Protein Binding, Recurrence, SARS-CoV-2/genetics, Spike Glycoprotein, Coronavirus/genetics, Vero Cells

Identifiers

Local EPrints ID: 451890
URI: http://eprints.soton.ac.uk/id/eprint/451890
ISSN: 2211-1247
PURE UUID: df528cb7-efbc-4efe-b302-9a565a2b6624
ORCID for Kordo Saeed: ORCID iD orcid.org/0000-0003-0123-0302
ORCID for Jacqui A. Prieto: ORCID iD orcid.org/0000-0002-5524-6775
ORCID for David A. Simpson: ORCID iD orcid.org/0000-0001-9072-5088
ORCID for Laura Baxter: ORCID iD orcid.org/0000-0003-0198-7591
ORCID for James W. Harrison: ORCID iD orcid.org/0000-0002-3643-0489
ORCID for Rebecca Brown: ORCID iD orcid.org/0000-0001-5825-6859
ORCID for Matthew Walker: ORCID iD orcid.org/0000-0001-6368-3644

Catalogue record

Date deposited: 02 Nov 2021 17:44
Last modified: 22 Jun 2022 02:06

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Contributors

Author: Bo Meng
Author: Steven A. Kemp
Author: Guido Papa
Author: Rawlings Datir
Author: Isabella A.T.M. Ferreira
Author: Sara Marelli
Author: William T. Harvey
Author: Spyros Lytras
Author: Ahmed Mohamed
Author: Giulia Gallo
Author: Nazia Thakur
Author: Dami A. Collier
Author: Petra Mlcochova
Author: Samuel C. Robson
Author: Rocio T. Martinez Nunez
Author: Kordo Saeed ORCID iD
Author: James G. Shepherd
Author: Matthew D. Parker
Author: Christopher R. Jones
Author: Christopher Holmes
Author: Thomas Williams
Author: Christopher Moore
Author: Hannah Paul
Author: Charlotte A. Williams
Author: Sarah Taylor
Author: Sophie Jones
Author: Laura Baxter ORCID iD
Author: Rachel Jones
Author: Jamie Young
Author: Minal Patel
Author: Louise Smith
Author: David G. Partridge
Author: James W. Harrison ORCID iD
Author: David Williams
Author: Clare Pearson
Author: Richard Gregory
Author: David J. Baker
Author: Rachel M. Tucker
Author: Rebecca Brown ORCID iD
Author: Elizabeth Cook
Author: Sarah Holmes
Author: Adam Jackson
Author: Matthew Jones
Author: David Robinson
Author: Mark Rose
Author: James Smith
Author: Robert Stanley
Author: Matthew Walker ORCID iD
Author: Kordo Saeed
Corporate Author: The COVID-19 Genomics UK (COG-UK) Consortium

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