Cell reports · 2022
SARS-CoV-2 Nsp13 encodes for an HLA-E-stabilizing peptide that abrogates inhibition of NKG2A-expressing NK cells.
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Hammer Quirin, Dunst Josefine, Christ Wanda, Picarazzi Francesca, Wendorff Mareike, Momayyezi Pouria, Huhn Oisín, Netskar Herman K, Maleki Kimia T, García Marina, Sekine Takuya, Sohlberg Ebba, Azzimato Valerio, Aouadi Myriam, Karolinska COVID-19 Study Group, Severe COVID-19 GWAS Group, Degenhardt Frauke, Franke Andre, Spallotta Francesco, Mori Mattia, Michaëlsson Jakob, Björkström Niklas K, Rückert Timo, Romagnani Chiara, Horowitz Amir, Klingström Jonas, Ljunggren Hans-Gustaf, Malmberg Karl-Johan
Аннотация
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.