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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.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Meng, Bo 
Kemp, Steven A 
Papa, Guido 
Ferreira, Isabella ATM 

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.

Description

Keywords

Alpha variant, B.1.1.7, COVID-19, SARS-CoV-2, antibody escape, deletion, infectivity, neutralizing antibodies, resistance, spike mutation, Animals, Antibodies, Neutralizing, Antibodies, Viral, COVID-19, Cell Line, Chlorocebus aethiops, HEK293 Cells, Humans, Immune Evasion, Mutation, Pandemics, Phylogeny, Protein Binding, Recurrence, SARS-CoV-2, Spike Glycoprotein, Coronavirus, Vero Cells

Journal Title

Cell Rep

Conference Name

Journal ISSN

2211-1247
2211-1247

Volume Title

35

Publisher

Elsevier BV
Sponsorship
NHS Blood and Transplant Trust Fund (WP15-02)
Medical Research Council (MR/P008801/1)
NHS Blood and Transplant (NHSBT) (WP15-02)
MRC (MC_PC_19027)
UK Research and Innovation (MC_PC_19027)
MRC (via Imperial College London) (MR/W005611/1)
COG-UK is supported by funding from the Medical Research Council (MRC), part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR), and Genome Research Limited, operating as the Wellcome Sanger Institute.
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