PMID- 34171266
OWN - NLM
STAT- MEDLINE
DCOM- 20210729
LR  - 20221031
IS  - 1934-6069 (Electronic)
IS  - 1931-3128 (Print)
IS  - 1931-3128 (Linking)
VI  - 29
IP  - 7
DP  - 2021 Jul 14
TI  - SARS-CoV-2 spike L452R variant evades cellular immunity and increases 
      infectivity.
PG  - 1124-1136.e11
LID - S1931-3128(21)00284-5 [pii]
LID - 10.1016/j.chom.2021.06.006 [doi]
AB  - 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.
CI  - Copyright (c) 2021 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Motozono, Chihiro
AU  - Motozono C
AD  - Division of Infection and Immunity, Joint Research Center for Human Retrovirus 
      Infection, Kumamoto University, Kumamoto 8600811, Japan.
FAU - Toyoda, Mako
AU  - Toyoda M
AD  - Division of Infection and Immunity, Joint Research Center for Human Retrovirus 
      Infection, Kumamoto University, Kumamoto 8600811, Japan.
FAU - Zahradnik, Jiri
AU  - Zahradnik J
AD  - Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, 
      Israel.
FAU - Saito, Akatsuki
AU  - Saito A
AD  - Department of Veterinary Science, Faculty of Agriculture, University of Miyazaki, 
      Miyazaki 8892192, Japan; Center for Animal Disease Control, University of 
      Miyazaki, Miyazaki 8892192, Japan; Graduate School of Medicine and Veterinary 
      Medicine, University of Miyazaki, Miyazaki 8892192, Japan.
FAU - Nasser, Hesham
AU  - Nasser H
AD  - Division of Molecular Virology and Genetics, Joint Research Center for Human 
      Retrovirus Infection, Kumamoto University, Kumamoto 8600811, Japan; Department of 
      Clinical Pathology, Faculty of Medicine, Suez Canal University, Ismailia 41511, 
      Egypt.
FAU - Tan, Toong Seng
AU  - Tan TS
AD  - Division of Infection and Immunity, Joint Research Center for Human Retrovirus 
      Infection, Kumamoto University, Kumamoto 8600811, Japan.
FAU - Ngare, Isaac
AU  - Ngare I
AD  - Division of Infection and Immunity, Joint Research Center for Human Retrovirus 
      Infection, Kumamoto University, Kumamoto 8600811, Japan.
FAU - Kimura, Izumi
AU  - Kimura I
AD  - Division of Systems Virology, Department of Infectious Disease Control, 
      International Research Center for Infectious Diseases, The Institute of Medical 
      Science, The University of Tokyo, Tokyo 1088639, Japan.
FAU - Uriu, Keiya
AU  - Uriu K
AD  - Division of Systems Virology, Department of Infectious Disease Control, 
      International Research Center for Infectious Diseases, The Institute of Medical 
      Science, The University of Tokyo, Tokyo 1088639, Japan.
FAU - Kosugi, Yusuke
AU  - Kosugi Y
AD  - Division of Systems Virology, Department of Infectious Disease Control, 
      International Research Center for Infectious Diseases, The Institute of Medical 
      Science, The University of Tokyo, Tokyo 1088639, Japan.
FAU - Yue, Yuan
AU  - Yue Y
AD  - Division of Molecular Virology and Genetics, Joint Research Center for Human 
      Retrovirus Infection, Kumamoto University, Kumamoto 8600811, Japan.
FAU - Shimizu, Ryo
AU  - Shimizu R
AD  - Division of Molecular Virology and Genetics, Joint Research Center for Human 
      Retrovirus Infection, Kumamoto University, Kumamoto 8600811, Japan.
FAU - Ito, Jumpei
AU  - Ito J
AD  - Division of Systems Virology, Department of Infectious Disease Control, 
      International Research Center for Infectious Diseases, The Institute of Medical 
      Science, The University of Tokyo, Tokyo 1088639, Japan.
FAU - Torii, Shiho
AU  - Torii S
AD  - Department of Molecular Virology, Research Institute for Microbial Diseases, 
      Osaka University, Osaka 5650871, Japan; Division of Microbiology and Immunology, 
      Center for Infectious Diseases Education and Research, Osaka University, Osaka 
      5650871, Japan; Laboratory of Virus Control, Research Institute for Microbial 
      Diseases, Osaka University, Osaka 5650871, Japan.
FAU - Yonekawa, Akiko
AU  - Yonekawa A
AD  - Department of Medicine and Biosystemic Science, Graduate School of Medical 
      Sciences, Kyushu University, Fukuoka 8128582, Japan.
FAU - Shimono, Nobuyuki
AU  - Shimono N
AD  - Department of Medicine and Biosystemic Science, Graduate School of Medical 
      Sciences, Kyushu University, Fukuoka 8128582, Japan.
FAU - Nagasaki, Yoji
AU  - Nagasaki Y
AD  - Division of Infectious Diseases, Clinical Research Institute, National 
      Hospitalization Organization, Kyushu Medical Center, Fukuoka 8108563, Japan.
FAU - Minami, Rumi
AU  - Minami R
AD  - Internal Medicine, Clinical Research Institute, National Hospital Organization, 
      Kyushu Medical Center, Fukuoka 8108563, Japan.
FAU - Toya, Takashi
AU  - Toya T
AD  - Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center 
      Komagome Hospital, Tokyo 1138677, Japan.
FAU - Sekiya, Noritaka
AU  - Sekiya N
AD  - Department of Infection Prevention and Control, Tokyo Metropolitan Cancer and 
      Infectious Diseases Center Komagome Hospital, Tokyo 1138677, Japan; Department of 
      Clinical Laboratory, Tokyo Metropolitan Cancer and Infectious Diseases Center 
      Komagome Hospital, Tokyo 1138677, Japan.
FAU - Fukuhara, Takasuke
AU  - Fukuhara T
AD  - Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido 
      University, Hokkaido 0608638, Japan.
FAU - Matsuura, Yoshiharu
AU  - Matsuura Y
AD  - Department of Molecular Virology, Research Institute for Microbial Diseases, 
      Osaka University, Osaka 5650871, Japan; Division of Microbiology and Immunology, 
      Center for Infectious Diseases Education and Research, Osaka University, Osaka 
      5650871, Japan; Laboratory of Virus Control, Research Institute for Microbial 
      Diseases, Osaka University, Osaka 5650871, Japan.
FAU - Schreiber, Gideon
AU  - Schreiber G
AD  - Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, 
      Israel.
CN  - Genotype to Phenotype Japan (G2P-Japan) Consortium
FAU - Ikeda, Terumasa
AU  - Ikeda T
AD  - Division of Molecular Virology and Genetics, Joint Research Center for Human 
      Retrovirus Infection, Kumamoto University, Kumamoto 8600811, Japan. Electronic 
      address: ikedat@kumamoto-u.ac.jp.
FAU - Nakagawa, So
AU  - Nakagawa S
AD  - Department of Molecular Life Science, Tokai University School of Medicine, 
      Kanagawa 2591193, Japan; CREST, Japan Science and Technology Agency, Saitama 
      3220012, Japan. Electronic address: so@tokai.ac.jp.
FAU - Ueno, Takamasa
AU  - Ueno T
AD  - Division of Infection and Immunity, Joint Research Center for Human Retrovirus 
      Infection, Kumamoto University, Kumamoto 8600811, Japan. Electronic address: 
      uenotaka@kumamoto-u.ac.jp.
FAU - Sato, Kei
AU  - Sato K
AD  - Division of Systems Virology, Department of Infectious Disease Control, 
      International Research Center for Infectious Diseases, The Institute of Medical 
      Science, The University of Tokyo, Tokyo 1088639, Japan; CREST, Japan Science and 
      Technology Agency, Saitama 3220012, Japan. Electronic address: 
      keisato@g.ecc.u-tokyo.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210615
PL  - United States
TA  - Cell Host Microbe
JT  - Cell host & microbe
JID - 101302316
RN  - 0 (Spike Glycoprotein, Coronavirus)
RN  - 0 (Viral Proteins)
RN  - 0 (spike protein, SARS-CoV-2)
RN  - EC 3.4.17.23 (ACE2 protein, human)
RN  - EC 3.4.17.23 (Angiotensin-Converting Enzyme 2)
SB  - IM
MH  - Angiotensin-Converting Enzyme 2
MH  - COVID-19/epidemiology/*virology
MH  - Genome, Viral
MH  - Humans
MH  - *Immunity, Cellular
MH  - Mutation
MH  - Phylogeny
MH  - Protein Binding
MH  - SARS-CoV-2/*genetics/*immunology
MH  - Spike Glycoprotein, Coronavirus/*genetics/*immunology
MH  - Viral Proteins/genetics
MH  - Virus Replication
PMC - PMC8205251
OTO - NOTNLM
OT  - B.1.1.298
OT  - B.1.427/429
OT  - COVID-19
OT  - L452R
OT  - SARS-CoV-2
OT  - Y453F
OT  - cellular immunity
OT  - naturally occurring variants
OT  - receptor-binding motif
OT  - spike protein
COIS- Declaration of interests The authors declare no competing interests.
EDAT- 2021/06/26 06:00
MHDA- 2021/07/30 06:00
PMCR- 2021/06/15
CRDT- 2021/06/25 20:10
PHST- 2021/04/13 00:00 [received]
PHST- 2021/05/22 00:00 [revised]
PHST- 2021/06/09 00:00 [accepted]
PHST- 2021/06/26 06:00 [pubmed]
PHST- 2021/07/30 06:00 [medline]
PHST- 2021/06/25 20:10 [entrez]
PHST- 2021/06/15 00:00 [pmc-release]
AID - S1931-3128(21)00284-5 [pii]
AID - 10.1016/j.chom.2021.06.006 [doi]
PST - ppublish
SO  - Cell Host Microbe. 2021 Jul 14;29(7):1124-1136.e11. doi: 
      10.1016/j.chom.2021.06.006. Epub 2021 Jun 15.