Abstract
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.
【초록키워드】 Mutation, neutralization, mutations, SARS-CoV-2 variant, Infection, sensitivity, Immune escape, L452R, spike gene, spike mutation, B.1.617, D614G, breakthrough infections, plasma, NTD, Breakthrough infection, spike mutations, mutant, USA, Pseudotyped viruses, N-terminal domain, Combination, Viral particles, vaccine-induced antibodies, sequences, sequence, coding region, circulating, viral particle, higher infectivity, neutralized, T19R, spike-pseudotyped viruses, raise, reported, addition, reduced, screened, exhibited, functional, introduced, changes in, contributed, spike-pseudotyped virus, 【제목키워드】 Mutation, SARS-CoV-2 spike, contribute,