SARS-CoV-2 spike L452R variant evades cellular immunity and increases infectivity.
Cell Host Microbe
; 29(7): 1124-1136.e11, 2021 07 14.
Article
in English
| MEDLINE | ID: covidwho-1272337
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
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Spike Glycoprotein, Coronavirus
/
SARS-CoV-2
/
COVID-19
/
Immunity, Cellular
Type of study:
Observational study
/
Randomized controlled trials
Topics:
Variants
Limits:
Humans
Language:
English
Journal:
Cell Host Microbe
Journal subject:
Microbiology
Year:
2021
Document Type:
Article
Affiliation country:
J.chom.2021.06.006
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