Meng B*, Kemp SA*, Papa G*, Datir R*, Ferriera IATM*, Marelli S, Harvey WT, Lytras S, Mohamed A, Gallo G, Thakur N, Collier DA, MIcochova P, The COVID-19 Genomics UK (COG-UK) Consortium, Duncan LM, Carabelli AM, Kenyon JC, Lever AM, De Marco A, Saliba C, Culap K, Cameroni E, Mathseon NJ, Piccoli L, Corti D, James LC, Robertson DL, Bailey D & Gupta RK (2021) Cell Reports. 35, 109292 DOI: 10.1016/j.celrep.2021.209292 *Contributed equally
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.