ArticleSignal transduction and targeted therapy2021
Sensing of cytoplasmic chromatin by cGAS activates innate immune response in SARS-CoV-2 infection.
Article in Signal transduction and targeted therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.
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Who cites it
76 citing papers in PubMed, 1 synthesis or guideline pooled it, 119 citations in OpenAlex.
- The cGAS-STING signaling pathway in the regulation of pulmonary infections: a systematic review.Frontiers in cellular and infection microbiology · 2025Pooled it
- Expulsion of nuclear DNA to the cytoplasm after viral entry: A mechanism for activation of the cGAS pathway.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Profilin-1 Deficiency Activates STING to Drive T Cell-Mediated Anti-Tumor Immunity in Breast Cancer.bioRxiv : the preprint server for biology · 2026Article
- Spike RBD drives sustained Parkinson's disease progression via microglia-neuron crosstalk-mediated RTP801 upregulation.Journal of advanced research · 2026Article
- Nanotechnology-driven STING regulation for on-demand therapy.Acta pharmaceutica Sinica. B · 2026Review
- The ORF6 accessory protein contributes to SARS-CoV-2 virulence and pathogenicity in the naturally susceptible feline model of infection.Journal of virology · 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
- STING agonist diABZI confers protection against swine acute diarrhea syndrome coronavirus in neonatal mice by activating antiviral immunity.Journal of virology · 2026Article
- RNA editing: an emerging frontier in cancer therapy - explorations, opportunities, and challenges.International journal of surgery (London, England) · 2026Article
- Emerging Strategies for Antitumor Immunotherapy and Antiviral Defense Through the cGAS-STING Pathway.International journal of nanomedicine · 2026Review
- Human coronavirus 3CL protease manipulates host protein STIM1 to facilitate immune evasion.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- SARS-CoV-2 innate immune recognition and implications for respiratory health.Cytokine & growth factor reviews · 2025Review
- Pattern Recognition Receptors (PRRs) Expression and Activation in COVID-19 and Long COVID: From SARS-CoV-2 Escape Mechanisms to Emerging PRR-Targeted Immunotherapies.Microorganisms · 2025Review
- The role of SARS-CoV-2 main protease in innate immune regulation: From molecular mechanisms to therapeutic implications.Acta pharmaceutica Sinica. B · 2025Review
- MERS-related coronavirus circulating in pangolins exhibits strong fusogenicity in human cells and high sensitivity to fusion inhibitors.Cell reports. Medicine · 2025Article
- Association ofLife (Basel, Switzerland) · 2025Article
- UNC0638 inhibits SARS-CoV-2 entry by blocking cathepsin L maturation.Journal of virology · 2025Article
- SARS-CoV-2 nucleocapsid protein directly prevents cGAS-DNA recognition through competitive binding.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Viral protease binds to nucleosomal DNA and cleaves nuclear cGAS that attenuates type I interferon.mBio · 2025Article
- Cytosolic nucleic acid sensing as driver of critical illness: mechanisms and advances in therapy.Signal transduction and targeted therapy · 2025Review
16 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The global coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a positive-sense RNA virus. How the host immune system senses and responds to SARS-CoV-2 infection remain largely unresolved. Here, we report that SARS-CoV-2 infection activates the innate immune response through the cytosolic DNA sensing cGAS-STING pathway. SARS-CoV-2 infection induces the cellular level of 2'3'-cGAMP associated with STING activation. cGAS recognizes chromatin DNA shuttled from the nucleus as a result of cell-to-cell fusion upon SARS-CoV-2 infection. We further demonstrate that the expression of spike protein from SARS-CoV-2 and ACE2 from host cells is sufficient to trigger cytoplasmic chromatin upon cell fusion. Furthermore, cytoplasmic chromatin-cGAS-STING pathway, but not MAVS-mediated viral RNA sensing pathway, contributes to interferon and pro-inflammatory gene expression upon cell fusion. Finally, we show that cGAS is required for host antiviral responses against SARS-CoV-2, and a STING-activating compound potently inhibits viral replication. Together, our study reported a previously unappreciated mechanism by which the host innate immune system responds to SARS-CoV-2 infection, mediated by cytoplasmic chromatin from the infected cells. Targeting the cytoplasmic chromatin-cGAS-STING pathway may offer novel therapeutic opportunities in treating COVID-19. In addition, these findings extend our knowledge in host defense against viral infection by showing that host cells' self-nucleic acids can be employed as a "danger signal" to alarm the immune system.
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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.