학술논문
SARS-CoV-2 Nsp13 encodes for an HLA-E-stabilizing peptide that abrogates inhibition of NKG2A-expressing NK cells
Document Type
article
Author
Quirin Hammer; Josefine Dunst; Wanda Christ; Francesca Picarazzi; Mareike Wendorff; Pouria Momayyezi; Oisín Huhn; Herman K. Netskar; Kimia T. Maleki; Marina García; Takuya Sekine; Ebba Sohlberg; Valerio Azzimato; Myriam Aouadi; Frauke Degenhardt; Andre Franke; Francesco Spallotta; Mattia Mori; Jakob Michaëlsson; Niklas K. Björkström; Timo Rückert; Chiara Romagnani; Amir Horowitz; Jonas Klingström; Hans-Gustaf Ljunggren; Karl-Johan Malmberg
Source
Cell Reports, Vol 38, Iss 10, Pp 110503- (2022)
Subject
Language
English
ISSN
2211-1247
Abstract
Summary: Natural killer (NK) cells are innate immune cells that contribute to host defense against virus infections. NK cells respond to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro and are activated in patients with acute coronavirus disease 2019 (COVID-19). However, by which mechanisms NK cells detect SARS-CoV-2-infected cells remains largely unknown. Here, we show that the Non-structural protein 13 of SARS-CoV-2 encodes for a peptide that is presented by human leukocyte antigen E (HLA-E). In contrast with self-peptides, the viral peptide prevents binding of HLA-E to the inhibitory receptor NKG2A, thereby rendering target cells susceptible to NK cell attack. In line with these observations, NKG2A-expressing NK cells are particularly activated in patients with COVID-19 and proficiently limit SARS-CoV-2 replication in infected lung epithelial cells in vitro. Thus, these data suggest that a viral peptide presented by HLA-E abrogates inhibition of NKG2A+ NK cells, resulting in missing self-recognition.