Subtopic Deep Dive

cGAS-STING Pathway in DNA Virus Sensing
Research Guide

What is cGAS-STING Pathway in DNA Virus Sensing?

The cGAS-STING pathway detects cytosolic DNA from DNA viruses through cGAS binding to DNA, activating STING to trigger type I interferon production and antiviral immune responses.

cGAS senses double-stranded DNA in the cytosol, producing cGAMP that binds and activates STING on the ER membrane (Çivril et al., 2013). STING activation recruits TBK1 and IRF3, leading to IFN-β transcription and interferon-stimulated gene expression (Schoggins et al., 2013). Over 10 foundational papers from 2013-2014 and 10 recent papers with 881-2649 citations define this pathway in viral sensing.

Curated Papers

Key Challenges

Why It Matters

cGAS-STING activation controls DNA virus infections by inducing interferons that restrict viral replication (McNab et al., 2015; Barber, 2015). Dysregulation links to autoimmunity and cancer, with Trex1 exonuclease preventing excessive sensing during radiotherapy to boost immunogenicity (Vanpouille-Box et al., 2017). Therapeutic targeting modulates inflammation in infections and tumors (Decout et al., 2021; Kwon and Bakhoum, 2019). Mitochondrial DNA stress via cGAS-STING primes antiviral states (West et al., 2015).

Key Research Challenges

Viral Evasion Mechanisms

DNA viruses recruit cofactors like those in HIV-1 to evade cGAS-STING detection (Rasaiyaah et al., 2013). Balancing evasion and host response remains unclear in multiple viruses. Schoggins et al. (2013) highlight pan-viral IFN gene roles requiring deeper dissection.

Pathway Hyperactivation Risks

Excessive cGAS-STING signaling causes autoimmunity and inflammation (Decout et al., 2021). Distinguishing viral from self-DNA sensing poses challenges (West et al., 2015). Therapeutic inhibition must avoid impairing antiviral defense (Barber, 2015).

Therapeutic Specificity

Targeting STING for cancer immunotherapy risks off-target inflammation (Kwon and Bakhoum, 2019). Radiotherapy-induced Trex1 regulation affects immunogenicity variably (Vanpouille-Box et al., 2017). Clinical translation needs precise agonists/antagonists (Decout et al., 2021).

Essential Papers

Type I interferons in infectious disease

Finlay W. McNab, Katrin D. Mayer-Barber, Alan Sher et al. · 2015 · Nature reviews. Immunology · 2.6K citations

Necroptosis, pyroptosis and apoptosis: an intricate game of cell death

Damien Bertheloot, Eicke Latz, Bernardo S. Franklin · 2021 · Cellular and Molecular Immunology · 2.0K citations

The cGAS–STING pathway as a therapeutic target in inflammatory diseases

Alexiane Decout, Jason D. Katz, Shankar Venkatraman et al. · 2021 · Nature reviews. Immunology · 1.9K citations

Mitochondrial DNA stress primes the antiviral innate immune response

A. Phillip West, William Khoury-Hanold, Matthew Staron et al. · 2015 · Nature · 1.8K citations

DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity

Claire Vanpouille‐Box, Amandine Alard, Molykutty J. Aryankalayil et al. · 2017 · Nature Communications · 1.6K citations

RIG-I-like receptors: their regulation and roles in RNA sensing

Jan Rehwinkel, Michaela U. Gack · 2020 · Nature reviews. Immunology · 1.6K citations

STING: infection, inflammation and cancer

Glen N. Barber · 2015 · Nature reviews. Immunology · 1.2K citations

Reading Guide

Foundational Papers

Start with Schoggins et al. (2013, 881 citations) for cGAS in pan-viral IFN induction and Çivril et al. (2013, 821 citations) for structural mechanism, as they establish core detection and activation steps.

Recent Advances

Study Decout et al. (2021, 1949 citations) for therapeutic targeting and West et al. (2015, 1759 citations) for mtDNA priming to grasp clinical and regulatory advances.

Core Methods

Core techniques include cGAMP production assays, STING knockout screens (Schoggins et al., 2013), X-ray crystallography for cGAS-DNA complexes (Çivril et al., 2013), and Trex1 modulation in immunogenicity models (Vanpouille-Box et al., 2017).

How PapersFlow Helps You Research cGAS-STING Pathway in DNA Virus Sensing

Discover & Search

Research Agent uses searchPapers and exaSearch to find 250M+ papers on cGAS-STING in DNA viruses, then citationGraph maps connections from Schoggins et al. (2013, 881 citations) to recent works like Decout et al. (2021). findSimilarPapers expands to related IFN responses.

Analyze & Verify

Analysis Agent applies readPaperContent to extract cGAS activation mechanisms from Çivril et al. (2013), verifies claims with CoVe chain-of-verification, and runs PythonAnalysis on IFN gene expression data from Schoggins et al. (2014) using pandas for statistical validation with GRADE scoring.

Synthesize & Write

Synthesis Agent detects gaps in viral evasion literature via contradiction flagging across Barber (2015) and Rasaiyaah et al. (2013); Writing Agent uses latexEditText, latexSyncCitations for pathway diagrams, and latexCompile for publication-ready reviews with exportMermaid for STING signaling flowcharts.

Use Cases

"Analyze IFN gene expression datasets from cGAS-STING papers for DNA virus specificity"

Research Agent → searchPapers → Analysis Agent → runPythonAnalysis (pandas/matplotlib on Schoggins et al. 2013 data) → statistical plots and p-values exported as CSV.

"Draft a LaTeX review on cGAS-STING therapeutic targeting in viral infections"

Synthesis Agent → gap detection → Writing Agent → latexEditText + latexSyncCitations (Decout et al. 2021, Barber 2015) → latexCompile → PDF with citations and figures.

"Find code for simulating cGAS DNA binding models from pathway papers"

Research Agent → paperExtractUrls → Code Discovery → paperFindGithubRepo → githubRepoInspect → executable scripts for STING activation kinetics.

Automated Workflows

Deep Research workflow scans 50+ cGAS-STING papers via searchPapers → citationGraph → structured report on DNA virus sensing evolution from Çivril et al. (2013). DeepScan applies 7-step CoVe analysis with GRADE to verify therapeutic claims in Decout et al. (2021). Theorizer generates hypotheses on STING modulation from Schoggins et al. (2013) and West et al. (2015).

Try Doxa for cGAS-STING Pathway in DNA Virus Sensing Research

Frequently Asked Questions

What defines the cGAS-STING pathway in DNA virus sensing?

cGAS binds cytosolic dsDNA from viruses, synthesizes cGAMP, activates STING, TBK1, and IRF3 for type I IFN production (Çivril et al., 2013; Schoggins et al., 2013).

What are key methods for studying cGAS-STING?

Structural biology reveals cGAS-DNA binding (Çivril et al., 2013); pan-viral IFN gene screens identify cGAS roles (Schoggins et al., 2013); mitochondrial DNA assays test priming (West et al., 2015).

What are landmark papers?

Foundational: Schoggins et al. (2013, 881 citations) on pan-viral cGAS roles; Çivril et al. (2013, 821 citations) on cGAS structure. Recent: Decout et al. (2021, 1949 citations) on therapeutics; West et al. (2015, 1759 citations) on mtDNA.

What open problems exist?

Viral evasion strategies need mapping beyond HIV-1 (Rasaiyaah et al., 2013); balancing anti-viral efficacy with autoimmunity risks in STING agonists (Decout et al., 2021); tissue-specific pathway regulation.