ArticleProceedings of the National Academy of Sciences of the United States of America2015
Modulation of the cGAS-STING DNA sensing pathway by gammaherpesviruses.
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 226 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
226 citing papers in PubMed, 1 synthesis or guideline pooled it, 315 citations in OpenAlex.
- Epstein-Barr virus-driven immunosuppression in nasopharyngeal carcinoma: a comprehensive review of viral mechanisms, spatial tumor ecosystems, and precision therapeutics.Frontiers in immunology · 2026Pooled it
- The Significance of cGAS-STING Signaling in Response to Oncogenic Viruses.Cell biochemistry and function · 2026Review
- VRK3 promotes KSHV infection by suppressing the antiviral type I interferon response.PLoS pathogens · 2026Article
- Roles of the cGAS-STING signaling pathway in viral latency.Journal of virology · 2026Review
- STING agonists as antiviral agents.FEBS letters · 2026Review
- Interferon-β induction heterogeneity during KSHV infection is correlated to levels and activation of the transcription factors ATF2 and RelA, and not IRF3.PLoS pathogens · 2026Article
- Targeting the cGAS-STING Pathway in Gastrointestinal Cancers: Modulating Tumor-associated Inflammation for Therapeutic Effect.Current drug targets · 2026Review
- cGAS-STING pathway in innate immunity and its cell-specific role in kidney diseases.Frontiers in immunology · 2026Review
- STING inhibits viral lytic reactivation and cell growth in primary effusion lymphoma.Frontiers in immunology · 2026Article
- [Correlation analysis of cell-free DNA in gingival crevicular fluid with periodontal clinical indicators and cyclic guanosine phosphate-adenosine phosphate synthase-stimulator of interferon genes signaling pathway].Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology · 2025Article
- Temporally integrated multiomics analysis elucidates intricate regulatory mechanisms of ASFV in a wild boar lung-derived clonal cell line.Veterinary research · 2025Article
- Extracellular vesicles derived EBV tegument protein BRRF2 suppresses cGAS phase separation to promote anti-viral innate immune evasion.Nature communications · 2025Article
- Interferon-β induction heterogeneity during KSHV infection is correlated to levels and activation of the transcription factors ATF2 and RelA, and not IRF3.bioRxiv : the preprint server for biology · 2025Article
- Essential function of the integrator complex in Kaposi's sarcoma-associated herpesvirus lytic replication.Journal of virology · 2025Article
- 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
- Model Systems of Gammaherpesvirus Infection, Immunity, and Disease.Journal of medical virology · 2025Review
- KSHV miRNAs target STING to evade innate immunity and facilitate KSHV lytic reactivation from latency.Cell reports · 2025Article
- Demystifying the cGAS-STING pathway: precision regulation in the tumor immune microenvironment.Molecular cancer · 2025Review
- Review
- Marek's disease virus protein kinase US3 inhibits DNA-sensing antiviral innate immunity via abrogating activation of NF-κB.Microbiology spectrum · 2025Article
166 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Infection of cells with DNA viruses triggers innate immune responses mediated by DNA sensors. cGMP-AMP synthase (cGAS) is a key DNA sensor that produces the cyclic dinucleotide cGMP-AMP (cGAMP) upon activation, which binds to and activates stimulator of interferon genes (STING), leading to IFN production and an antiviral response. Kaposi's sarcoma-associated herpesvirus (KSHV) is a DNA virus that is linked to several human malignancies. We report that KSHV infection activates the cGAS-STING pathway, and that cGAS and STING also play an important role in regulating KSHV reactivation from latency. We screened KSHV proteins for their ability to inhibit this pathway and identified six viral proteins that block IFN-β activation through this pathway. This study is the first report identifying multiple viral proteins encoded by a human DNA virus that inhibit the cGAS-STING DNA sensing pathway. One such protein, viral interferon regulatory factor 1 (vIRF1), targets STING by preventing it from interacting with TANK binding kinase 1 (TBK1), thereby inhibiting STING's phosphorylation and concomitant activation, resulting in an inhibition of the DNA sensing pathway. Our data provide a unique mechanism for the negative regulation of STING-mediated DNA sensing. Moreover, the depletion of vIRF1 in the context of KSHV infection prevented efficient viral reactivation and replication, and increased the host IFN response to KSHV. The vIRF1-expressing cells also inhibited IFN-β production following infection with DNA pathogens. Collectively, our results demonstrate that gammaherpesviruses encode inhibitors that block cGAS-STING-mediated antiviral immunity, and that modulation of this pathway is important for viral transmission and the lifelong persistence of herpesviruses in the human population.
Indexed as
Identifiers
What OpenQuestion 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 OpenQuestion graph.