SARS-CoV-2 peptides bind to NKG2D and increase NK cell activity

• Published in: Cellular immunology Vol. 371; p. 104454
• Main Authors: Kim, Hanna, Byun, Jae-Eun, Yoon, Suk Ran, Koohy, Hashem, Jung, Haiyoung, Choi, Inpyo
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.01.2022; The Author(s). Published by Elsevier Inc
• Subjects: Amino Acid Sequence; Cell Line, Tumor; COVID-19 - immunology; COVID-19 - metabolism; COVID-19 - virology; Cytotoxicity; Cytotoxicity, Immunologic - immunology; Humans; IFN-γ; Interferon-gamma - immunology; Interferon-gamma - metabolism; Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; Lung - immunology; Lung - pathology; Lung - virology; Lymphocyte Activation - immunology; NK Cell Lectin-Like Receptor Subfamily K - immunology; NK Cell Lectin-Like Receptor Subfamily K - metabolism; NKG2D; Peptide; Peptides - immunology; Peptides - metabolism; Protein Binding; Research Paper; SARS-Cov-2; SARS-CoV-2 - immunology; SARS-CoV-2 - metabolism; SARS-CoV-2 - physiology; Signal Transduction - immunology; Spike Glycoprotein, Coronavirus - chemistry; Spike Glycoprotein, Coronavirus - immunology; Spike Glycoprotein, Coronavirus - metabolism; Cytotoxicity; SARS-Cov-2; NKG2D; IFN-γ; NK; Peptide
• ISSN: 0008-8749; 1090-2163
• DOI: 10.1016/j.cellimm.2021.104454

•Understanding the crosstalk between SARS-CoV-2 and the innate immune system.•Two SARS-CoV-2 S protein peptides capable of binding to the NKG2D receptor of natural killer (NK) cells are identified.•These peptides activate NK cells and stimulate IFN-γ production. Immune dysregulation is commonly observed in patients with coronavirus disease 2019 (COVID-19). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces severe lung inflammation and innate immune cell dysregulation. However, the precise interaction between SARS-CoV-2 and the innate immune system is currently unknown. To understand the interaction between SARS-CoV-2 and natural killer (NK) cells, several SARS-CoV-2 S protein peptides capable of binding to the NKG2D receptor were screened by in silico analysis. Among them, two peptides, cov1 and cov2, bound to NK cells and NKG2D receptors. These cov peptides increased NK cytotoxicity toward lung cancer cells, stimulated interferon gamma (IFN-γ) production by NK cells, and likely mediated these responses through the phosphorylation of Vav1, a key downstream-signaling molecule of NKG2D and NK activation genes. The direct interaction between SARS-CoV-2 and NK cells is a novel finding, and modulation of this interaction has potential clinical application as a therapeutic target for COVID-19.