ArticleiScience2021
SARS-CoV-2, SARS-CoV-1, and HIV-1 derived ssRNA sequences activate the NLRP3 inflammasome in human macrophages through a non-classical pathway.
Article in iScience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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Who cites it
83 citing papers in PubMed, 117 citations in OpenAlex.
- Porcine coronavirus promotes NLRP3 inflammasome activation during virus-induced neuroinflammation.mBio · 2026Article
- PANoptosis as a Therapeutic Target for COVID-19.Current microbiology · 2026Review
- Defective RNA Polymerase III sensing of mitochondrial DNA in pulmonary epithelial cells impairs type I IFN immunity to SARS-CoV-2.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Neuroinflammation and NeuroHIV: understanding the role of HIV-1 related factors in microglial activation.Translational psychiatry · 2026Review
- HIV gp120 induces TREM1 expression through TLR-PGE₂ signalling in human monocyte-derived microglia.Journal of neuroinflammation · 2026Article
- Comparative progress on the mechanisms of airway mucosal injury induced by different pathogens: SARS-CoV-2, influenza A virus, and Mycoplasma pneumoniae.Frontiers in cellular and infection microbiology · 2026Review
- SARS-CoV-2 variants: biology, pathogenicity, immunity and control.Nature reviews. Microbiology · 2026Review
- Article
- Comprehensive mapping of the signaling events evoked by SARS-CoV-2 variants delta and omicron in human astrocytes.Scientific reports · 2025Article
- In Vitro Investigation of Statin Effects on Genes Associated with Severe COVID-19 in Cancerous and Non-Cancerous Cells.Biomedicines · 2025Article
- Toll-like receptor 7 (TLR7)-mediated antiviral response protects mice from lethal SARS-CoV-2 infection.Journal of virology · 2025Article
- Targeting inflammasomes as a therapeutic potential for HIV/AIDS.Cellular and molecular life sciences : CMLS · 2025Review
- Cytosolic nucleic acid sensing as driver of critical illness: mechanisms and advances in therapy.Signal transduction and targeted therapy · 2025Review
- NLRP3 inflammasome activation in astrocytes restricts SARS-CoV-2 through gasdermin-D-driven IL-1β release.Frontiers in immunology · 2025Article
- Immunogenic cell death-related signature predicts prognosis and immunotherapy efficacy in bladder cancer.Translational cancer research · 2024Article
- Review
- The IRE1α-XBP1 arm of the unfolded protein response is a host factor activated in SARS-CoV-2 infection.Biochimica et biophysica acta. Molecular basis of disease · 2024Article
- Harnessing the power of IFN for therapeutic approaches to COVID-19.Journal of virology · 2024Review
- SARS-CoV-2 and its ORF3a, E and M viroporins activate inflammasome in human macrophages and induce of IL-1α in pulmonary epithelial and endothelial cells.Cell death discovery · 2024Article
- SARS-CoV-2 biology and host interactions.Nature reviews. Microbiology · 2024Review
23 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Macrophages promote an early host response to infection by releasing pro-inflammatory cytokines such as interleukin-1β (IL-1β), TNF, and IL-6. The bioactivity of IL-1β is classically dependent on NLRP3 inflammasome activation, which culminates in caspase-1 activation and pyroptosis. Recent studies suggest a role for NLRP3 inflammasome activation in lung inflammation and fibrosis in both COVID-19 and SARS, and there is evidence of NLRP3 involvement in HIV-1 disease. Here, we show that GU-rich single-stranded RNA (GU-rich RNA) derived from SARS-CoV-2, SARS-CoV-1, and HIV-1 trigger a TLR8-dependent pro-inflammatory cytokine response from human macrophages in the absence of pyroptosis, with GU-rich RNA from the SARS-CoV-2 spike protein triggering the greatest inflammatory response. Using genetic and pharmacological inhibition, we show that the induction of mature IL-1β is through a non-classical pathway dependent on caspase-1, caspase-8, the NLRP3 inflammasome, potassium efflux, and autophagy while being independent of TRIF (TICAM1), vitamin D3, and pyroptosis.
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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.