tetano
Editor, Senior Moderator
Cell Rep
. 2022 Feb 21;110503.
doi: 10.1016/j.celrep.2022.110503. Online ahead of print.
SARS-CoV-2 Nsp13 encodes for an HLA-E-stabilizing peptide that abrogates inhibition of NKG2A-expressing NK cells
Quirin Hammer[SUP] 1 [/SUP], Josefine Dunst[SUP] 2 [/SUP], Wanda Christ[SUP] 3 [/SUP], Francesca Picarazzi[SUP] 4 [/SUP], Mareike Wendorff[SUP] 5 [/SUP], Pouria Momayyezi[SUP] 3 [/SUP], Oisín Huhn[SUP] 3 [/SUP], Herman K Netskar[SUP] 6 [/SUP], Kimia T Maleki[SUP] 3 [/SUP], Marina García[SUP] 3 [/SUP], Takuya Sekine[SUP] 3 [/SUP], Ebba Sohlberg[SUP] 3 [/SUP], Valerio Azzimato[SUP] 3 [/SUP], Myriam Aouadi[SUP] 3 [/SUP], Karolinska COVID-19 Study Group; Severe COVID-19 GWAS Group; Frauke Degenhardt[SUP] 5 [/SUP], Andre Franke[SUP] 5 [/SUP], Francesco Spallotta[SUP] 7 [/SUP], Mattia Mori[SUP] 4 [/SUP], Jakob Michaëlsson[SUP] 3 [/SUP], Niklas K Björkström[SUP] 3 [/SUP], Timo Rückert[SUP] 8 [/SUP], Chiara Romagnani[SUP] 9 [/SUP], Amir Horowitz[SUP] 10 [/SUP], Jonas Klingström[SUP] 3 [/SUP], Hans-Gustaf Ljunggren[SUP] 3 [/SUP], Karl-Johan Malmberg[SUP] 11 [/SUP]
Affiliations
Abstract
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[SUP]+[/SUP] NK cells, resulting in missing self-recognition.
Keywords: COVID-19; HLA-E; NK cells; NKG2A; SARS-CoV-2; missing self.
. 2022 Feb 21;110503.
doi: 10.1016/j.celrep.2022.110503. Online ahead of print.
SARS-CoV-2 Nsp13 encodes for an HLA-E-stabilizing peptide that abrogates inhibition of NKG2A-expressing NK cells
Quirin Hammer[SUP] 1 [/SUP], Josefine Dunst[SUP] 2 [/SUP], Wanda Christ[SUP] 3 [/SUP], Francesca Picarazzi[SUP] 4 [/SUP], Mareike Wendorff[SUP] 5 [/SUP], Pouria Momayyezi[SUP] 3 [/SUP], Oisín Huhn[SUP] 3 [/SUP], Herman K Netskar[SUP] 6 [/SUP], Kimia T Maleki[SUP] 3 [/SUP], Marina García[SUP] 3 [/SUP], Takuya Sekine[SUP] 3 [/SUP], Ebba Sohlberg[SUP] 3 [/SUP], Valerio Azzimato[SUP] 3 [/SUP], Myriam Aouadi[SUP] 3 [/SUP], Karolinska COVID-19 Study Group; Severe COVID-19 GWAS Group; Frauke Degenhardt[SUP] 5 [/SUP], Andre Franke[SUP] 5 [/SUP], Francesco Spallotta[SUP] 7 [/SUP], Mattia Mori[SUP] 4 [/SUP], Jakob Michaëlsson[SUP] 3 [/SUP], Niklas K Björkström[SUP] 3 [/SUP], Timo Rückert[SUP] 8 [/SUP], Chiara Romagnani[SUP] 9 [/SUP], Amir Horowitz[SUP] 10 [/SUP], Jonas Klingström[SUP] 3 [/SUP], Hans-Gustaf Ljunggren[SUP] 3 [/SUP], Karl-Johan Malmberg[SUP] 11 [/SUP]
Affiliations
- PMID: 35235832
- DOI: 10.1016/j.celrep.2022.110503
Abstract
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[SUP]+[/SUP] NK cells, resulting in missing self-recognition.
Keywords: COVID-19; HLA-E; NK cells; NKG2A; SARS-CoV-2; missing self.