Abstract
SARS-CoV-2 Spike amino acid replacements in the receptor binding domain (RBD) occur relatively frequently and some have a consequence for immune recognition. Here we report recurrent emergence and significant onward transmission of a six-nucleotide deletion in the S gene, which results in loss of two amino acids: H69 and V70. Of particular note this deletion, ΔH69/V70, often co-occurs with the receptor binding motif amino acid replacements N501Y, N439K and Y453F. One of the ΔH69/V70+ N501Y lineages, B.1.1.7, is comprised of over 4000 SARS-CoV-2 genome sequences from the UK and includes eight other S gene mutations: RBD (N501Y and A570D), S1 (ΔH69/V70 and Δ144/145) and S2 (P681H, T716I, S982A and D1118H). Some of these mutations have presumably arisen as a result of the virus evolving from immune selection pressure in infected individuals and at least one, lineage B.1.1.7, potentially from a chronic infection. Given our recent evidence that ΔH69/V70 enhances viral infectivity (Kemp et al. 2020), its effect on virus fitness appears to be independent to the RBD changes. Enhanced surveillance for the ΔH69/V70 deletion with and without RBD mutations should be considered as a priority. Permissive mutations such as ΔH69/V70 have the potential to enhance the ability of SARS-CoV-2 to generate new variants, including vaccine escape variants, that would have otherwise significantly reduced viral infectivity.
Competing Interest Statement
RKG has received consulting fees from UMOVIS lab, Gilead Sciences and ViiV Healthcare, and a research grant from InvisiSmart Technologies.
Footnotes
↵6 https://www.cogconsortium.uk. Full list of consortium names and affiliations are in Appendix 1.
Author affiliation has been corrected