|
Basic Characteristics of Mutations
|
|
Mutation Site
|
L452R |
|
Mutation Site Sentence
|
SARS-CoV-2 spike L452R variant evades cellular immunity and increases infectivity. |
|
Mutation Level
|
Amino acid level |
|
Mutation Type
|
Nonsynonymous substitution |
|
Gene/Protein/Region
|
S |
|
Standardized Encoding Gene
|
S
|
|
Genotype/Subtype
|
B.1.427;B.1.429;B.1.617 |
|
Viral Reference
|
-
|
|
Functional Impact and Mechanisms
|
|
Disease
|
COVID-19
|
|
Immune
|
- |
|
Target Gene
|
-
|
|
Clinical and Epidemiological Correlations
|
|
Clinical Information
|
- |
|
Treatment
|
- |
|
Location
|
- |
|
Literature Information
|
|
PMID
|
34171266
|
|
Title
|
SARS-CoV-2 spike L452R variant evades cellular immunity and increases infectivity
|
|
Author
|
Motozono C,Toyoda M,Zahradnik J,Saito A,Nasser H,Tan TS,Ngare I,Kimura I,Uriu K,Kosugi Y,Yue Y,Shimizu R,Ito J,Torii S,Yonekawa A,Shimono N,Nagasaki Y,Minami R,Toya T,Sekiya N,Fukuhara T,Matsuura Y,Schreiber G,Ikeda T,Nakagawa S,Ueno T,Sato K
|
|
Journal
|
Cell host & microbe
|
|
Journal Info
|
2021 Jul 14;29(7):1124-1136
|
|
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.
|
|
Sequence Data
|
-
|
|
|