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

Cell Rep. 2021 Jun 29;35(13):109292. doi: 10.1016/j.celrep.2021.109292. Epub 2021 Jun 8.

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.

Keywords: Alpha variant; B.1.1.7; COVID-19; SARS-CoV-2; antibody escape; deletion; infectivity; neutralizing antibodies; resistance; spike mutation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology
  • COVID-19 / immunology*
  • COVID-19 / virology*
  • Cell Line
  • Chlorocebus aethiops
  • HEK293 Cells
  • Humans
  • Immune Evasion
  • Mutation
  • Pandemics
  • Phylogeny
  • Protein Binding
  • Recurrence
  • SARS-CoV-2 / genetics*
  • SARS-CoV-2 / immunology
  • Spike Glycoprotein, Coronavirus / genetics*
  • Spike Glycoprotein, Coronavirus / immunology*
  • Vero Cells

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Spike Glycoprotein, Coronavirus

Supplementary concepts

  • SARS-CoV-2 variants