ArticleThe EMBO journal2021
SARS-CoV-2 sensing by RIG-I and MDA5 links epithelial infection to macrophage inflammation.
Article in The EMBO journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 156 papers, 1 of them a synthesis that pooled it.
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Who cites it
156 citing papers in PubMed, 1 synthesis or guideline pooled it, 226 citations in OpenAlex.
- Meta-analysis of Transcriptomic Data from Lung Autopsy and Cellular Models of SARS-CoV-2 Infection.Biochemical genetics · 2024Pooled it
- Preclinical and randomized phase I studies of plitidepsin in adults hospitalized with COVID-19.Life science alliance · 2022Trial
- TOR3A represses type I interferon production and limits viral clearance during respiratory syncytial virus infection.Emerging microbes & infections · 2026Article
- Gapmers targeting conserved SARS-CoV-2 single-stranded regions reduce viral load and reshape inflammatory macrophage responses.iScience · 2026Article
- Establishing the molecular basis for MDA5 mutation-linked autoimmunity.Nucleic acids research · 2026Article
- Loss of cellular RNA homeostasis contributes to MDA5 activation during virus infection.Nature immunology · 2026Article
- Coronavirus Nsp15 endoribonuclease: linking viral RNA regulation to immune evasion and viral fitness.Journal of virology · 2026Review
- Alternative splicing broadens antiviral diversity at the human OAS2 locus.The EMBO journal · 2026Article
- Efferocytosis of apoptotic bodies drives SARS-CoV-2 infection and macrophage inflammation.Nature communications · 2026Article
- Modulation of Host Innate Immune Response by Highly Pathogenic Human Coronaviruses during Viral Infection.Journal of microbiology and biotechnology · 2026Review
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- The ORF6 accessory protein contributes to SARS-CoV-2 virulence and pathogenicity in the naturally susceptible feline model of infection.Journal of virology · 2026Article
- 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
- SARS-CoV-2 Nsp15 facilitates immune evasion and viral replication by limiting multiple host innate immune pathways, including cGAS-STING.The Journal of general virology · 2026Article
- Article
- Macrophage makeover extreme viral edition: mechanisms of immune subversion and therapeutic perspectives.The Journal of general virology · 2026Review
- Stealth replication of SARS-CoV-2 Omicron in the nasal epithelium at physiological temperature.Journal of virology · 2026Article
- Article
- SARS-CoV-2-induced damage to rat cortical neuronal networks ex vivo is mediated by the pro-inflammatory activation of the cGAS-STING pathway.Journal of neurovirology · 2025Article
- Comprehensive mapping of the signaling events evoked by SARS-CoV-2 variants delta and omicron in human astrocytes.Scientific reports · 2025Article
96 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
SARS-CoV-2 infection causes broad-spectrum immunopathological disease, exacerbated by inflammatory co-morbidities. A better understanding of mechanisms underpinning virus-associated inflammation is required to develop effective therapeutics. Here, we discover that SARS-CoV-2 replicates rapidly in lung epithelial cells despite triggering a robust innate immune response through the activation of cytoplasmic RNA sensors RIG-I and MDA5. The inflammatory mediators produced during epithelial cell infection can stimulate primary human macrophages to enhance cytokine production and drive cellular activation. Critically, this can be limited by abrogating RNA sensing or by inhibiting downstream signalling pathways. SARS-CoV-2 further exacerbates the local inflammatory environment when macrophages or epithelial cells are primed with exogenous inflammatory stimuli. We propose that RNA sensing of SARS-CoV-2 in lung epithelium is a key driver of inflammation, the extent of which is influenced by the inflammatory state of the local environment, and that specific inhibition of innate immune pathways may beneficially mitigate inflammation-associated COVID-19.
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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.