Interrogating the natural killer cell response to COVID-19: SARS-CoV-2 modulates ligands for NK cell receptors & escapes NK cell killing
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Severe coronavirus disease 2019 (COVID-19) induces strong alterations in the peripheral immune system. Some immune cell types take on a protective role in this disease, while others contribute to disease pathology. One cell type whose functional role in COVID-19 is not yet known is the natural killer (NK) cell. To investigate this question, we assessed the ability of primary NK cells to respond to A549-ACE2 cells infected with replication-competent SARS-CoV-2, the causative agent of COVID-19. We found striking differences in the ability of NK cells to recognize and kill SARS-CoV-2-infected cells compared to bystander cells. To determine the mechanistic basis for our observations, we interrogated the expression of ligands for NK cell receptors on infected cells and identified significant modulation of multiple ligands on SARS-CoV-2-infected cells. Finally, we screened individual SARS-CoV-2 proteins for the ability to modulate NK cell responses. Collectively, our work reveals that infection of target cells with SARS-CoV-2 alters the NK cell response and elucidates a mechanism by which this may occur.