SARS-CoV-2 spike L452R variant evades cellular immunity and increases infectivity.

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. Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Chihiro Motozono, Mako Toyoda, Jiri Zahradnik, Akatsuki Saito, Hesham Nasser, Toong Seng Tan, Isaac Ngare, Izumi Kimura, Keiya Uriu, Yusuke Kosugi, Yuan Yue, Ryo Shimizu, Jumpei Ito, Shiho Torii, Akiko Yonekawa, Nobuyuki Shimono, Yoji Nagasaki, Rumi Minami, Takashi Toya, Noritaka Sekiya, Takasuke Fukuhara, Yoshiharu Matsuura, Gideon Schreiber, Genotype to Phenotype Japan (G2P-Japan) Consortium, Terumasa Ikeda, So Nakagawa, Takamasa Ueno, Kei Sato. SARS-CoV-2 spike L452R variant evades cellular immunity and increases infectivity. Cell host & microbe. 2021 Jul 14;29(7):1124-1136.e11

Mesh Tags

Substances

PMID: 34171266

search → result