ArticleAntimicrobial agents and chemotherapy2015
STING agonists induce an innate antiviral immune response against hepatitis B virus.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
72 citing papers in PubMed, 1 synthesis or guideline pooled it, 117 citations in OpenAlex.
- Molecular mechanisms and therapeutic strategies of cGAS-STING pathway in liver disease: the quest continues.Frontiers in immunology · 2025Pooled it
- The diversity of STING in regulating immune cell function and its role in liver diseases: from bench to bedside.Cell & bioscience · 2026Review
- A Novel Host-Based Immunotherapy for the Suppression of HBV and HCV Replication: Heat-KilledCells · 2026Article
- The role of the cGAS-STING pathway in male reproductive disorders.Molecular biology reports · 2026Review
- Quercetin potentially suppresses HBV activity through targeting the RIG-I/MAVS pathway.iScience · 2026Article
- Targeting the Cyclic GMP-AMP Synthase-Stimulator of Interferon Genes Pathway: An Emerging Therapeutic Strategy for Digestive Diseases.Clinical and translational gastroenterology · 2026Review
- STING agonists as antiviral agents.FEBS letters · 2026Review
- Hepatocyte-Derived Apoptotic Bodies as Pathological Intercellular Messengers in the Liver.Biomolecules · 2026Review
- Antiviral and immune modulatory activities of STING agonists in a mouse model of persistent hepatitis B virus infection.PLoS pathogens · 2025Article
- Review
- Progress Update on STING Agonists as Vaccine Adjuvants.Vaccines · 2025Review
- Targeting cGAS-STING: modulating the immune landscape of hepatic diseases.Frontiers in immunology · 2025Review
- Nucleos(t)ide analogues potentially activate T lymphocytes through inducing interferon expression in hepatic cells and patients with chronic hepatitis B.Scientific reports · 2024Article
- Review
- Hypermethylation of the glutathione peroxidase 4 gene promoter is associated with the occurrence of immune tolerance phase in chronic hepatitis B.Virology journal · 2024Article
- Activation of Stimulator of Interferon Genes (STING): Promising Strategy to Overcome Immune Resistance in Prostate Cancer.Current medicinal chemistry · 2024Review
- Progress of cGAS-STING signaling pathway-based modulation of immune response by traditional Chinese medicine in clinical diseases.Frontiers in immunology · 2024Review
- Unlocking STING as a Therapeutic Antiviral Strategy.International journal of molecular sciences · 2023Review
- Current understanding of the cGAS-STING signaling pathway: Structure, regulatory mechanisms, and related diseases.Zoological research · 2023Review
- Nanocarriers for effective delivery: modulation of innate immunity for the management of infections and the associated complications.Journal of nanobiotechnology · 2022Review
12 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
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Chronicity of hepatitis B virus (HBV) infection is due to the failure of a host to mount a sufficient immune response to clear the virus. The aim of this study was to identify small-molecular agonists of the pattern recognition receptor (PRR)-mediated innate immune response to control HBV infection. To achieve this goal, a coupled mouse macrophage and hepatocyte culture system mimicking the intrahepatic environment was established and used to screen small-molecular compounds that activate macrophages to produce cytokines, which in turn suppress HBV replication in a hepatocyte-derived stable cell line supporting HBV replication in a tetracycline-inducible manner. An agonist of the mouse stimulator of interferon (IFN) genes (STING), 5,6-dimethylxanthenone-4-acetic acid (DMXAA), was found to induce a robust cytokine response in macrophages that efficiently suppressed HBV replication in mouse hepatocytes by reducing the amount of cytoplasmic viral nucleocapsids. Profiling of cytokines induced by DMXAA and agonists of representative Toll-like receptors (TLRs) in mouse macrophages revealed that, unlike TLR agonists that induced a predominant inflammatory cytokine/chemokine response, the STING agonist induced a cytokine response dominated by type I IFNs. Moreover, as demonstrated in an HBV hydrodynamic mouse model, intraperitoneal administration of DMXAA significantly induced the expression of IFN-stimulated genes and reduced HBV DNA replication intermediates in the livers of mice. This study thus proves the concept that activation of the STING pathway induces an antiviral cytokine response against HBV and that the development of small-molecular human STING agonists as immunotherapeutic agents for treatment of chronic hepatitis B is warranted.
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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.