ArticleScientific reports2020
Toll-like receptor dual-acting agonists are potent inducers of PBMC-produced cytokines that inhibit hepatitis B virus production in primary human hepatocytes.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Extended analysis on peripheral blood cytokines correlated with hepatitis B virus viral load in chronically infected patients - a systematic review and meta-analysis.Frontiers in medicine · 2024Pooled it
- Using exploratory pharmacokinetic and pharmacodynamic analyses to predict the probability of flu-like symptoms in healthy volunteers and patients with chronic hepatitis B treated with the toll-like receptor 7 agonist ruzotolimod.Clinical and translational science · 2024Trial
- Probing Immune Signatures of Conjugated Pattern Recognition Receptor Ligands Identifies Chimeras with Potent Adjuvant and Antitumor Activities.Journal of medicinal chemistry · 2026Article
- Navigating the Viral Hepatitis Drug Landscape: New Discoveries and Enduring Challenges. A Narrative Review.Infectious diseases and therapy · 2026Review
- The role of toll-like receptor 7 signaling in mice infected by severe fever with thrombocytopenia syndrome virus.Scientific reports · 2026Article
- STING agonists trigger monocyte death via apoptosis, pyroptosis, caspase-8 activation and mitochondrial dysfunction.Cell death discovery · 2025Article
- Where does ISAC (immune-stimulating antibody conjugates) go from here?Journal for immunotherapy of cancer · 2025Review
- Current status and challenges of therapeutic targets, novel drugs and delivery systems for hepatitis B: how far to our goal?Frontiers in cellular and infection microbiology · 2025Review
- From bark to bench: innovations in QS-21 adjuvant characterization and manufacturing.Frontiers in immunology · 2025Review
- 3D engineered tissue models for studying human-specific infectious viral diseases.Bioactive materials · 2023Review
- Locking and Unlocking Thrombin Function Using Immunoquiescent Nucleic Acid Nanoparticles with Regulated RetentionNano letters · 2022Article
- Understanding Immune Responses to Viruses-Do Underlying Th1/Th2 Cell Biases Predict Outcome?Viruses · 2022Review
- Article
- [Rational selection of virologic and immunological biomarkers and therapeutic endpoints in the clinical trials of new drugs treating chronic hepatitis B].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2022Article
- NLRX1 can counteract innate immune response induced by an external stimulus favoring HBV infection by competitive inhibition of MAVS-RLRs signaling in HepG2-NTCP cells.Science progress · 2021Article
- Toll-Like Receptor Response to Hepatitis B Virus Infection and Potential of TLR Agonists as Immunomodulators for Treating Chronic Hepatitis B: An Overview.International journal of molecular sciences · 2021Review
- Review
- Innate immunity and HBV persistence.Current opinion in virology · 2021Review
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recombinant interferon-α (IFN-α) treatment functionally cures chronic hepatitis B virus (HBV) infection in some individuals and suppresses virus replication in hepatocytes infected in vitro. We studied the antiviral effect of conditioned media (CM) from peripheral blood mononuclear cells (PBMCs) stimulated with agonists of Toll-like receptors (TLRs) 2, 7, 8 and 9. We found that CM from PBMCs stimulated with dual-acting TLR7/8 (R848) and TLR2/7 (CL413) agonists were more potent drivers of inhibition of HBe and HBs antigen secretion from HBV-infected primary human hepatocytes (PHH) than CM from PBMCs stimulated with single-acting TLR7 (CL264) or TLR9 (CpG-B) agonists. Inhibition of HBV in PHH did not correlate with the quantity of PBMC-produced IFN-α, but it was a complex function of multiple secreted cytokines. More importantly, we found that the CM that efficiently inhibited HBV production in freshly isolated PHH via various cytokine repertoires and mechanisms did not reduce covalently closed circular (ccc)DNA levels. We confirmed our data with a cell culture model based on HepG2-NTCP cells and the plasmacytoid dendritic cell line GEN2.2. Collectively, our data show the importance of dual-acting TLR agonists inducing broad cytokine repertoires. The development of poly-specific TLR agonists provides novel opportunities towards functional HBV cure.
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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.