Cell Reports (Mar 2022)
SARS-CoV-2 Nsp13 encodes for an HLA-E-stabilizing peptide that abrogates inhibition of NKG2A-expressing NK cells
- 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
Affiliations
- Quirin Hammer
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden; Corresponding author
- Josefine Dunst
- Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden; Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden
- Wanda Christ
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden
- Francesca Picarazzi
- Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena, Italy
- Mareike Wendorff
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany
- Pouria Momayyezi
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden
- Oisín Huhn
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden
- Herman K. Netskar
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway
- Kimia T. Maleki
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden
- Marina García
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden
- Takuya Sekine
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden
- Ebba Sohlberg
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden
- Valerio Azzimato
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden
- Myriam Aouadi
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden
- Frauke Degenhardt
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany
- Andre Franke
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany
- Francesco Spallotta
- Institute for Systems Analysis and Computer Science “A. Ruberti,” National Research Council (IASI–CNR), Rome, Italy
- Mattia Mori
- Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena, Italy
- Jakob Michaëlsson
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden
- Niklas K. Björkström
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden
- Timo Rückert
- Innate Immunity, Deutsches Rheuma-Forschungszentrum (DRFZ), Institute of the Leibniz Association, Berlin, Germany
- Chiara Romagnani
- Innate Immunity, Deutsches Rheuma-Forschungszentrum (DRFZ), Institute of the Leibniz Association, Berlin, Germany; Division of Gastroenterology, Infectiology and Rheumatology, Medical Department I, Charité–Universitätsmedizin Berlin, Berlin, Germany
- Amir Horowitz
- Department of Oncological Sciences, Precision Immunology Institute, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Jonas Klingström
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden
- Hans-Gustaf Ljunggren
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden
- Karl-Johan Malmberg
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden; Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway
- Journal volume & issue
-
Vol. 38,
no. 10
p. 110503
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.
