SARS-CoV-2 Nsp13 encodes for an HLA-E-stabilizing peptide that abrogates inhibition of NKG2A-expressing NK cells
Hammer, Quirin; Dunst, Josefine; Christ, Wanda; Picarazzi, Francesca; Wendorff, Mareike; Momayyezi, Pouria; Huhn, Oisín; Netskar, Herman Krogstad; Maleki, Kimia T.; García, Marina; Sekine, Takuya; Sohlberg, Ebba; Azzimato, Valerio; Aouadi, Myriam; Holten, Aleksander Rygh; Kildal, Anders Benjamin; Lind, Andreas; Dyrhol-Riise, Anne Ma; Hoff, Dag Arne Lihaug; Solligård, Erik; Holter, Jan Cato; Afset, Jan Egil; Damås, Jan Kristian; Hov, Johannes Espolin Roksund; Bergan, Jonas; Risnes, Kari; Muller, Karl Erik; Tonby, Kristian; Heggelund, Lars; Gustad, Lise Tuset; Grimsrud, Marit Mæhle; Vadla, May Sissel; Lenning, Ole Bernt; Myhre, Ronny; Haider, Sammra; Dudman, Susanne Gjeruldsen; Karlsen, Tom Hemming; Folseraas, Trine; Skogen, Vegard; 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
Peer reviewed, Journal article
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Original versionCell reports. 2022, 38 (10), . 10.1016/j.celrep.2022.110503
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.