ArticleCell reports2022
SARS-CoV-2 escapes direct NK cell killing through Nsp1-mediated downregulation of ligands for NKG2D.
Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 43 citations in OpenAlex.
- Natural killer cells against viral infection: from basic biology to immunotherapy.Precision clinical medicine · 2026Review
- The Expanding Role of HLA-E in Host Defense: A Target for Broadly Applicable Vaccines and Immunotherapies.Cells · 2025Review
- MICBG406A polymorphism reduces risk of mechanical ventilation and death during viral acute lung injury.JCI insight · 2025Article
- SARS-CoV-2 nsp1 mediates broad inhibition of translation in mammals.Cell reports · 2025Article
- Impact of SARS-CoV-2 Wuhan and Omicron Variant Proteins on Type I Interferon Response.Viruses · 2025Article
- The HLA-B -21 M/T dimorphism associates with disease severity in COVID-19.Genes and immunity · 2025Article
- From natural defenders to therapeutic warriors: NK cells in HIV immunotherapy.Immunotherapy · 2025Review
- SARS-CoV-2 infection induces adaptive NK cell responses by spike protein-mediated induction of HLA-E expression.Emerging microbes & infections · 2024Article
- Article
- SARS-CoV-2 N protein-induced Dicer, XPO5, SRSF3, and hnRNPA3 downregulation causes pneumonia.Nature communications · 2024Article
- NK-cell receptor modulation in viral infections.Clinical and experimental immunology · 2024Review
- Article
- Article
- Forty years of HIV research inspires the development of SARS-CoV-2 therapy.Journal of molecular cell biology · 2024Article
- A genome-wide association study for survival from a multi-centre European study identified variants associated with COVID-19 risk of death.Scientific reports · 2024Article
- Elevated levels of cell-free NKG2D-ligands modulate NKG2D surface expression and compromise NK cell function in severe COVID-19 disease.Frontiers in immunology · 2024Article
- SARS-CoV-2 viral persistence in lung alveolar macrophages is controlled by IFN-γ and NK cells.Nature immunology · 2023Article
- Defining the role of natural killer cells in COVID-19.Nature immunology · 2023Review
- Association of inhibitory NKG2A and activating NKG2D natural killer cell receptor genes with resistance to SARS-CoV-2 infection in a western Indian population.Archives of virology · 2023Article
- COVID-19 Biogenesis and Intracellular Transport.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Natural killer (NK) cells are cytotoxic effector cells that target and lyse virally infected cells; many viruses therefore encode mechanisms to escape such NK cell killing. Here, we interrogate the ability of SARS-CoV-2 to modulate NK cell recognition and lysis of infected cells. We find that NK cells exhibit poor cytotoxic responses against SARS-CoV-2-infected targets, preferentially killing uninfected bystander cells. We demonstrate that this escape is driven by downregulation of ligands for the activating receptor NKG2D (NKG2D-L). Indeed, early in viral infection, prior to NKG2D-L downregulation, NK cells are able to target and kill infected cells; however, this ability is lost as viral proteins are expressed. Finally, we find that SARS-CoV-2 non-structural protein 1 (Nsp1) mediates downregulation of NKG2D-L and that Nsp1 alone is sufficient to confer resistance to NK cell killing. Collectively, our work demonstrates that SARS-CoV-2 evades direct NK cell cytotoxicity and describes a mechanism by which this occurs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.