ArticleProceedings of the National Academy of Sciences of the United States of America2015
cGAS-mediated stabilization of IFI16 promotes innate signaling during herpes simplex virus infection.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 192 papers.
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Who cites it
192 citing papers in PubMed, 251 citations in OpenAlex.
- The cGAS-STING/MITA pathway in innate antiviral immunity and beyond.Cell insight · 2026Review
- Isoliquiritigenin Elicits Potent Antiviral Activity Against Pseudorabies Virus Through Modulating the cGAS/STING and JAK/STAT Signaling Cascades.Veterinary sciences · 2026Article
- The Significance of cGAS-STING Signaling in Response to Oncogenic Viruses.Cell biochemistry and function · 2026Review
- 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
- The ISG Atlas: a loss-of-function analysis characterizes antiviral properties of interferon stimulated genes.Nature communications · 2026Article
- The cGAS-STING pathway in cancer: friend or foe.Cell death & disease · 2026Review
- Z-DNA binding protein 1 mediates necroptotic cell death in primary murine microglia following herpes simplex virus-1 infection.Journal of neurovirology · 2026Article
- Opportunities and challenges of targeting cGAS-STING in cancer.Nature reviews. Cancer · 2026Review
- HSV-2 genome recognition by nuclear cGAS instigates IFN-β production and influences inflammasome activation duringFrontiers in immunology · 2026Article
- PYHIN proteins: guardians or contributors to hepatitis B virus pathogenesis?Frontiers in immunology · 2026Review
- Structural insights into the atypical filament assembly of pyrin domain-containing IFI16.The EMBO journal · 2025Article
- Mitochondrial dysfunction acts as a modulator of the immunometabolic route for activating the cytosolic DNA sensor pathway in triggering innate immunosurveillance.Journal of translational medicine · 2025Review
- Activation and regulation of cGAS-STING signaling in cancer cells.Molecular cell · 2025Review
- Article
- AIM2 and IFI16 as nucleic acid sensors in Periodontitis-Driven systemic inflammation: emerging evidence and therapeutic implications.Clinical oral investigations · 2025Review
- Deciphering cGAS-STING signaling: implications for tumor immunity and hepatocellular carcinoma.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- IRF1 amplifies HSV-1-triggered antiviral innate immunity in a feed-forward manner.Cell insight · 2025Article
- The cGAS-STING axis: a comprehensive review from immune defense to disease pathogenesis.Immunologic research · 2025Review
- The Epithelial Immune Response to Human Papillomavirus Infection.Pathogens (Basel, Switzerland) · 2025Review
- Regulation of the innate immune response in human neurons by ICP34.5 maintains herpes simplex virus 1 latency.bioRxiv : the preprint server for biology · 2025Article
132 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Interferon γ-inducible protein 16 (IFI16) and cGMP-AMP synthase (cGAS) have both been proposed to detect herpesviral DNA directly in herpes simplex virus (HSV)-infected cells and initiate interferon regulatory factor-3 signaling, but it has been unclear how two DNA sensors could both be required for this response. We therefore investigated their relative roles in human foreskin fibroblasts (HFFs) infected with HSV or transfected with plasmid DNA. siRNA depletion studies showed that both are required for the production of IFN in infected HFFs. We found that cGAS shows low production of cGMP-AMP in infected cells, but instead cGAS is partially nuclear in normal human fibroblasts and keratinocytes, interacts with IFI16 in fibroblasts, and promotes the stability of IFI16. IFI16 is associated with viral DNA and targets to viral genome complexes, consistent with it interacting directly with viral DNA. Our results demonstrate that IFI16 and cGAS cooperate in a novel way to sense nuclear herpesviral DNA and initiate innate signaling.
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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.