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SARS-CoV-2 Spike 1 Protein Controls Natural Killer Cell Activation via the HLA-E/NKG2A Pathway
| Content Provider | MDPI |
|---|---|
| Author | Bortolotti, Daria Gentili, Valentina Rizzo, Sabrina Rotola, Antonella Rizzo, Roberta |
| Copyright Year | 2020 |
| Description | Natural killer cells are important in the control of viral infections. However, the role of NK cells during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has previously not been identified. Peripheral blood NK cells from SARS-CoV and SARS-CoV-2 naïve subjects were evaluated for their activation, degranulation, and interferon-gamma expression in the presence of SARS-CoV and SARS-CoV-2 spike proteins. K562 and lung epithelial cells were transfected with spike proteins and co-cultured with NK cells. The analysis was performed by flow cytometry and immune fluorescence. SARS-CoV and SARS-CoV-2 spike proteins did not alter NK cell activation in a K562 in vitro model. On the contrary, SARS-CoV-2 spike 1 protein (SP1) intracellular expression by lung epithelial cells resulted in NK cell-reduced degranulation. Further experiments revealed a concomitant induction of HLA-E expression on the surface of lung epithelial cells and the recognition of an SP1-derived HLA-E-binding peptide. Simultaneously, there was increased modulation of the inhibitory receptor NKG2A/CD94 on NK cells when SP1 was expressed in lung epithelial cells. We ruled out the GATA3 transcription factor as being responsible for HLA-E increased levels and HLA-E/NKG2A interaction as implicated in NK cell exhaustion. We show for the first time that NK cells are affected by SP1 expression in lung epithelial cells via HLA-E/NKG2A interaction. The resulting NK cells’ exhaustion might contribute to immunopathogenesis in SARS-CoV-2 infection. |
| Starting Page | 1975 |
| e-ISSN | 20734409 |
| DOI | 10.3390/cells9091975 |
| Journal | Cells |
| Issue Number | 9 |
| Volume Number | 9 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2020-08-26 |
| Access Restriction | Open |
| Subject Keyword | Cells Immunology Sars-cov-2 Nk Cell Nkg2a Hla-e |
| Content Type | Text |
| Resource Type | Article |
