ArticleProceedings of the National Academy of Sciences of the United States of America2020
DNA-induced 2'3'-cGAMP enhances haplotype-specific human STING cleavage by dengue protease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- Mitochondria-targeted MXene-based nanozymes promote mitophagy and inhibit mtDNA-triggered cGAS/STING inflammation in osteoarthritis.Bioactive materials · 2026Article
- Extracellular cGAMP in health and disease.Molecular biomedicine · 2026Review
- The cGAS-STING pathway and mitochondrial metabolism: from mechanistic insights to therapeutic potential in tumor.Journal of translational medicine · 2026Review
- Chloroquine Enhances Mitochondrial Antiviral Signaling-Mediated Cytokine Induction and Alters Mitochondrial Morphology.Journal of innate immunity · 2026Article
- cGAS-STING signaling pathway as a therapeutic target in human diseases.Chinese medical journal · 2025Review
- Multifunctional nanoparticles and collagenase dual loaded thermosensitive hydrogel system for enhanced tumor-penetration, reversed immune suppression and photodynamic-immunotherapy.Bioactive materials · 2025Article
- Bioinformatic characterization of STING expression in hematological malignancies reveals association with prognosis and anti-tumor immunity.Frontiers in immunology · 2025Article
- Sophora tonkinensis enhances activation of cGAS-STING pathway and restrains HBV replication.Frontiers in pharmacology · 2025Article
- Mitophagy and cGAS-STING crosstalk in neuroinflammation.Acta pharmaceutica Sinica. B · 2024Review
- SIRT2 negatively regulates the cGAS-STING pathway by deacetylating G3BP1.EMBO reports · 2023Article
- Defective Mitochondrial Quality Control during Dengue Infection Contributes to Disease Pathogenesis.Journal of virology · 2022Article
- Glycosylation and S-palmitoylation regulate SARS-CoV-2 spike protein intracellular trafficking.iScience · 2022Article
- Review
- Generation and Characterization of Human-Mouse STING Chimeras That Allow DENV Replication in Mouse Cells.mSphere · 2022Article
- STING promotes senescence, apoptosis, and extracellular matrix degradation in osteoarthritis via the NF-κB signaling pathway.Cell death & disease · 2021Article
- The Regulatory Network of Cyclic GMP-AMP Synthase-Stimulator of Interferon Genes Pathway in Viral Evasion.Frontiers in microbiology · 2021Review
- Running With Scissors: Evolutionary Conflicts Between Viral Proteases and the Host Immune System.Frontiers in immunology · 2021Review
- Recent Insights Into the Molecular Mechanism of Toll-Like Receptor Response to Dengue Virus Infection.Frontiers in microbiology · 2021Review
- Innate Immune DNA Sensing of Flaviviruses.Viruses · 2020Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cytosolic DNA sensor cGMP-AMP synthase (cGAS) synthesizes the noncanonical cyclic dinucleotide 2'3'-cGAMP to activate the adaptor protein stimulator of IFN genes (STING), thus awakening host immunity in response to DNA pathogen infection. However, dengue virus (DENV), an RNA virus without a DNA stage in its life cycle, also manipulates cGAS-STING-mediated innate immunity by proteolytic degradation of STING. Here, we found that the sensitivity of STING to DENV protease varied with different human STING haplotypes. Exogenous DNA further enhanced DENV protease's ability to interact and cleave protease-sensitive STING. DNA-enhanced STING cleavage was reduced in cGAS-knockdown cells and triggered by the cGAS product 2'3'-cGAMP. The source of DNA may not be endogenous mitochondrial DNA but rather exogenous reactivated viral DNA. Cells producing 2'3'-cGAMP by overexpressing cGAS or with DNA virus reactivation enhanced STING cleavage in neighboring cells harboring DENV protease. DENV infection reduced host innate immunity in cells with the protease-sensitive STING haplotype, whose homozygote genotype frequency was found significantly reduced in Taiwanese people with dengue fever. Therefore, the human STING genetic background and DNA pathogen coinfection may be the missing links contributing to DENV pathogenesis.
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