RT Journal Article
SR Electronic
T1 SARS-CoV-2 spike E156G/Δ157-158 mutations contribute to increased infectivity and immune escape
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202201415
DO 10.26508/lsa.202201415
VO 5
IS 7
A1 Tarun Mishra
A1 Rishikesh Dalavi
A1 Garima Joshi
A1 Atul Kumar
A1 Pankaj Pandey
A1 Sanjeev Shukla
A1 Ram K Mishra
A1 Ajit Chande
YR 2022
UL https://www.life-science-alliance.org/content/5/7/e202201415.abstract
AB Breakthrough infections by emerging SARS-CoV-2 variants raise significant concerns. Here, we sequence-characterized the spike gene from breakthrough infections that corresponded to B.1.617 sublineage. Delineating the functional impact of spike mutations revealed that N-terminal domain (NTD)-specific E156G/Δ157-158 contributed to increased infectivity and reduced sensitivity to vaccine-induced antibodies. A six-nucleotide deletion (467–472) in the spike-coding region introduced this change in the NTD. We confirmed the presence of E156G/Δ157-158 from cases concurrently screened, in addition to other circulating spike (S1) mutations such as T19R, T95I, L452R, E484Q, and D614G. Notably, E156G/Δ157-158 was present in more than 90% of the sequences reported from the USA and UK in October 2021. The spike-pseudotyped viruses bearing a combination of E156G/Δ157-158 and L452R exhibited higher infectivity and reduced sensitivity to neutralization. Notwithstanding, the post-recovery plasma robustly neutralized viral particles bearing the mutant spike. When the spike harbored E156G/Δ157-158 along with L452R and E484Q, increased cell-to-cell fusion was also observed, suggesting a combinatorial effect of these mutations. Our study underscores the importance of non-RBD changes in determining infectivity and immune escape.