Cell Host & Microbe
Volume 29, Issue 7, 14 July 2021, Pages 1124-1136.e11
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Short Article
SARS-CoV-2 spike L452R variant evades cellular immunity and increases infectivity

https://doi.org/10.1016/j.chom.2021.06.006Get rights and content
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open access

Highlights

  • L452R and Y453F mutations in the SARS-CoV-2 spike RBM have emerged

  • L452R and Y453F mutants escape HLA-A24-restricted cellular immunity

  • L452R increases viral infectivity and fusogenicity and promotes viral replication

Summary

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

SARS-CoV-2
COVID-19
cellular immunity
spike protein
receptor-binding motif
naturally occurring variants
B.1.427/429
B.1.1.298
L452R
Y453F

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These authors contributed equally

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