ArticleCells2020
SARS-CoV-2 Spike 1 Protein Controls Natural Killer Cell Activation via the HLA-E/NKG2A Pathway.
Article in Cells, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
73 citing papers in PubMed, 1 synthesis or guideline pooled it, 116 citations in OpenAlex.
- Cardiac biomarkers, cardiac injury, and comorbidities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis.Immunity, inflammation and disease · 2021Pooled it
- Natural killer cells against viral infection: from basic biology to immunotherapy.Precision clinical medicine · 2026Review
- SARS-CoV-2 Infection Associated with HHV-6A Reactivation and an Inhibitory KIR2DL2/HLA-C1 Immunogenetic Profile.Microorganisms · 2026Article
- The Expanding Role of HLA-E in Host Defense: A Target for Broadly Applicable Vaccines and Immunotherapies.Cells · 2025Review
- Soluble SARS-CoV-2 Spike glycoprotein: considering some potential pathogenic effects.Frontiers in immunology · 2025Review
- The innate immune response in SARS-CoV2 infection: focus on toll-like receptor 4 in severe disease outcomes.Frontiers in immunology · 2025Review
- The Impact of Killer Cell Immunoglobulin-Like Receptors and Human Leukocyte Antigen-E, Human Leukocyte Antigen-G Polymorphisms on Innate Immunity and COVID-19 Severity.Journal of immunology research · 2025Article
- COVID-19 Induces Prolonged Immunological Exhaustion Leading to Relapse of Hematological Malignancies Except in Hematopoietic Cell Transplant Recipients.Mediterranean journal of hematology and infectious diseases · 2025Article
- SARS-CoV-2 infection induces adaptive NK cell responses by spike protein-mediated induction of HLA-E expression.Emerging microbes & infections · 2024Article
- NK-cell receptor modulation in viral infections.Clinical and experimental immunology · 2024Review
- Article
- Review
- SARS-CoV-2: A Glance at the Innate Immune Response Elicited by Infection and Vaccination.Antibodies (Basel, Switzerland) · 2024Review
- Unraveling the dynamic mechanisms of natural killer cells in viral infections: insights and implications.Virology journal · 2024Review
- TLR2/4 are novel activating receptors for SARS-CoV-2 spike protein on NK cells.Frontiers in immunology · 2024Article
- Ad5-nCoV Vaccination Could Induce HLA-E Restricted CD8Viruses · 2023Article
- 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
- Natural killer cells and their exosomes in viral infections and related therapeutic approaches: where are we?Cell communication and signaling : CCS · 2023Review
- The Potential of Probiotics as Ingestible Adjuvants and Immune Modulators for Antiviral Immunity and Management of SARS-CoV-2 Infection and COVID-19.Pathogens (Basel, Switzerland) · 2023Review
13 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
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.
Indexed as
Identifiers
What OpenQuestion holds
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.