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.
【저자키워드】 SARS-CoV-2, NK cell, HLA-E, NKG2A, 【초록키워드】 coronavirus, SARS-CoV, SARS-COV-2 infection, Infection, peptide, NK cells, viral infections, flow cytometry, immune, Spike protein, Protein, SARS-CoV-2 spike protein, Immunopathogenesis, experiment, expression, Lung epithelial cells, Blood, SARS-CoV-2 spike, natural killer cell, Interaction, Analysis, transcription factor, acute respiratory syndrome, Activation, modulation, SARS-CoV-2 spike proteins, contrary, in vitro model, inhibitory receptor, degranulation, GATA3, Alter, peripheral, SP1, responsible, resulting, affected, evaluated, was performed, contribute, expressed, implicated, lung epithelial cell, co-cultured, naïve subject, transfected with, was increased, 【제목키워드】 spike, Control, natural,