SARS-CoV-2 Nsp13 encodes for an HLA-E-stabilizing peptide that abrogates inhibition of NKG2A-expressing NK cells

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 mechan...

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Bibliographic Details
Published in:Cell reports (Cambridge) Vol. 38; no. 10; p. 110503
Main Authors: 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, 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
Format: Journal Article
Language:English
Published: United States Elsevier Inc 08.03.2022
The Author(s)
Elsevier
Subjects:
COVID-19
COVID-19 - immunology
Histocompatibility Antigens Class I - immunology
HLA-E
HLA-E Antigens
Humans
Killer Cells, Natural - immunology
Methyltransferases - immunology
missing self
NK Cell Lectin-Like Receptor Subfamily C - immunology
NK Cell Lectin-Like Receptor Subfamily C - metabolism
NK cells
NKG2A
Peptides - metabolism
RNA Helicases - immunology
SARS-CoV-2
Viral Nonstructural Proteins - immunology
COVID-19
NK cells
SARS-CoV-2
NKG2A
missing self
HLA-E
ISSN:2211-1247, 2211-1247
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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. [Display omitted] •SARS-CoV-2 Non-structural protein 13 encodes for an HLA-E-restricted peptide•HLA-E/Nsp13232–240 complexes do not bind to the inhibitory receptor NKG2A•Nsp13232–240 allows for NKG2A+ NK cell activation by missing self-recognition•NKG2A+ NK cells proficiently restrict SARS-CoV-2 replication in vitro Natural killer (NK) cells eliminate virus-infected cells. Hammer et al. show that SARS-CoV-2 encodes for a peptide that does not bind to an inhibitory receptor of NK cells, thereby facilitating NK cell activation. This missing self-recognition could enable NK cells to detect and kill SARS-CoV-2-infected cells.
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ISSN:2211-1247
2211-1247
DOI:10.1016/j.celrep.2022.110503