Abstract
Many SARS-CoV-2 variants with naturally acquired mutations have emerged. These mutations can affect viral properties such as infectivity and immune resistance. Although the sensitivity of naturally occurring SARS-CoV-2 variants to humoral immunity has been investigated, sensitivity to human leukocyte antigen (HLA)-restricted cellular immunity remains largely unexplored. Here, we demonstrate that two recently emerging mutations in the receptor-binding domain of the SARS-CoV-2 spike protein, L452R (in B.1.427/429 and B.1.617) and Y453F (in B.1.1.298), confer escape from HLA-A24-restricted cellular immunity. These mutations reinforce affinity toward the host entry receptor ACE2. Notably, the L452R mutation increases spike stability, viral infectivity, viral fusogenicity, and thereby promotes viral replication. These data suggest that HLA-restricted cellular immunity potentially affects the evolution of viral phenotypes and that a further threat of the SARS-CoV-2 pandemic is escape from cellular immunity.
Keywords: B.1.1.298; B.1.427/429; COVID-19; L452R; SARS-CoV-2; Y453F; cellular immunity; naturally occurring variants; receptor-binding motif; spike protein.
【저자키워드】 COVID-19, SARS-CoV-2, Spike protein, L452R, cellular immunity, Y453F, B.1.1.298, receptor-binding motif, B.1.427/429, naturally occurring variants, 【초록키워드】 Evolution, ACE2, pandemic, Mutation, SARS-CoV-2 pandemic, SARS-CoV-2 variant, human leukocyte antigen, Spike protein, Antigen, sensitivity, Humoral immunity, Viral, Receptor-binding domain, SARS-CoV-2 variants, viral infectivity, L452R, cellular immunity, Y453F, viral replication, B.1.617, SARS-CoV-2 spike protein, phenotype, escape, receptor-binding motif, affinity, cellular, leukocyte, These data, spike stability, entry receptor, immune resistance, Host, Affect, investigated, increase, promote, the receptor-binding domain, the SARS-CoV-2, 【제목키워드】 variant, SARS-CoV-2 spike, increase, evade,