ArticleCell death discovery2024
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.
Article in Cell death discovery, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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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.
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Who cites it
16 citing papers in PubMed, 16 citations in OpenAlex.
- Involvement of NLRP3 Inflammasome in Methamphetamine Augmentation of SARS-CoV-2 N-Protein-Induced Neuroinflammation in Rat Microglial Cells.International journal of molecular sciences · 2026Article
- Targeting SARS-CoV-2 Structural and Accessory Proteins: Emerging Opportunities for Small-Molecule Coronavirus Antivirals.Pharmaceutics · 2026Review
- Human Coronavirus 229E Uses ORF4/4a to Antagonize the Host Restriction Factor SERINC5.MedComm · 2026Article
- Modulation of Host Innate Immune Response by Highly Pathogenic Human Coronaviruses during Viral Infection.Journal of microbiology and biotechnology · 2026Review
- PANoptosis as a Therapeutic Target for COVID-19.Current microbiology · 2026Review
- Antiviral Inflammasomes and How to Find Them.Viruses · 2026Review
- The soluble G protein of respiratory syncytial virus promotes viral dissemination via TLR2-mediated NLRP3 priming and pyroptosis.Npj viruses · 2026Article
- Mammalian innate antiviral defenses: beyond interferon.Journal of virology · 2025Review
- Pyroptosis in Respiratory Virus Infections: A Narrative Review of Mechanisms, Pathophysiology, and Potential Therapeutic Interventions.Microorganisms · 2025Review
- Heterogeneous Evolution Among SARS-CoV-2 Genes and Variants of Concern.Journal of medical virology · 2025Article
- Pyroptosis, a double-edged sword during pathogen infection: a review.Cell death discovery · 2025Review
- A live attenuated SARS-CoV-2 vaccine constructed by dual inactivation of NSP16 and ORF3a.EBioMedicine · 2025Article
- Hidden players of COVID-19: the evolving roles of SARS-CoV-2 accessory proteins.Frontiers in immunology · 2025Review
- Article
- RACK1 and NEK7 mediate GSDMD-dependent macrophage pyroptosis upon Streptococcus suis infection.Veterinary research · 2024Article
- Beta Spike-Presenting SARS-CoV-2 Virus-like Particle Vaccine Confers Broad Protection against Other VOCs in Mice.Vaccines · 2024Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
Inflammasome assembly is a potent mechanism responsible for the host protection against pathogens, including viruses. When compromised, it can allow viral replication, while when disrupted, it can perpetuate pathological responses by IL-1 signaling and pyroptotic cell death. SARS-CoV-2 infection was shown to activate inflammasome in the lungs of COVID-19 patients, however, potential mechanisms responsible for this response are not fully elucidated. In this study, we investigated the effects of ORF3a, E and M SARS-CoV-2 viroporins in the inflammasome activation in major populations of alveolar sentinel cells: macrophages, epithelial and endothelial cells. We demonstrated that each viroporin is capable of activation of the inflammasome in macrophages to trigger pyroptosis-like cell death and IL-1α release from epithelial and endothelial cells. Small molecule NLRP3 inflammasome inhibitors reduced IL-1 release but weakly affected the pyroptosis. Importantly, we discovered that while SARS-CoV-2 could not infect the pulmonary microvascular endothelial cells it induced IL-1α and IL-33 release. Together, these findings highlight the essential role of macrophages as the major inflammasome-activating cell population in the lungs and point to endothelial cell expressed IL-1α as a potential novel component driving the pulmonary immunothromobosis in COVID-19.
Identifiers
What Socratic 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 Socratic graph.