ArticleJournal of virology2014
Inosine-mediated modulation of RNA sensing by Toll-like receptor 7 (TLR7) and TLR8.
Article in Journal of virology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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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
22 citing papers in PubMed, 35 citations in OpenAlex.
- IFN-λ4 Exhibits Differential Induction and Antiviral Activity in RSV and HMPV Infections.Viruses · 2026Article
- Deciphering the antiviral mechanisms of Fangqin Qinggan decoction against influenza A virus: a multi-omics and machine learning approach.Chinese medicine · 2025Article
- The Role of Chemical Modifications in the Genome of Negative-Sense RNA Viruses on the Innate Immune Response.Viruses · 2025Review
- The role of ADAR1 in human pathophysiology.Frontiers in cell and developmental biology · 2025Review
- Promotion of TLR7-MyD88-dependent inflammation and autoimmunity in mice through stem-loop changes in Lnc-Atg16l1.Nature communications · 2024Article
- Posttranscriptional Regulation by Proteins and Noncoding RNAs.Advances in experimental medicine and biology · 2024Article
- The regulation of antiviral innate immunity through non-mFrontiers in immunology · 2023Review
- Metabolomic and transcriptomic signatures of influenza vaccine response in healthy young and older adults.Aging cell · 2022Article
- The role of RNA editing enzyme ADAR1 in human disease.Wiley interdisciplinary reviews. RNA · 2022Review
- Adenosine Deaminases Acting on RNA (ADARs) and Viral Infections.Annual review of virology · 2021Article
- Pathogenesis-based preexposure prophylaxis associated with a low risk of SARS-CoV-2 infection in healthcare workers at a designated COVID-19 hospital: a pilot study.BMC infectious diseases · 2021Article
- Escape from X chromosome inactivation and female bias of autoimmune diseases.Molecular medicine (Cambridge, Mass.) · 2020Review
- It's the Little Things (in Viral RNA).mBio · 2020Review
- Disruption of Neutrophil Extracellular Traps (NETs) Links Mechanical Strain to Post-traumatic Inflammation.Frontiers in immunology · 2019Article
- The Role of Nucleic Acid Sensing in Controlling Microbial and Autoimmune Disorders.International review of cell and molecular biology · 2019Review
- Viruses Seen by Our Cells: The Role of Viral RNA Sensors.Journal of immunology research · 2018Review
- TLR8 activation and inhibition by guanosine analogs in RNA: Importance of functional groups and chain length.Bioorganic & medicinal chemistry · 2018Article
- Size, Shape, and Sequence-Dependent Immunogenicity of RNA Nanoparticles.Molecular therapy. Nucleic acids · 2017Article
- Review
- What can pestiviral endonucleases teach us about innate immunotolerance?Cytokine & growth factor reviews · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 8 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
RNA-specific adenosine deaminase (ADAR)-mediated adenosine-to-inosine (A-to-I) editing is a critical arm of the antiviral response. However, mechanistic insights into how A-to-I RNA editing affects viral infection are lacking. We posited that inosine incorporation into RNA facilitates sensing of nonself RNA by innate immune sensors and accordingly investigated the impact of inosine-modified RNA on Toll-like receptor 7 and 8 (TLR7/8) sensing. Inosine incorporation into synthetic single-stranded RNA (ssRNA) potentiated tumor necrosis factor alpha (TNF-α) or alpha interferon (IFN-α) production in human peripheral blood mononuclear cells (PBMCs) in a sequence-dependent manner, indicative of TLR7/8 recruitment. The effect of inosine incorporation on TLR7/8 sensing was restricted to immunostimulatory ssRNAs and was not seen with inosine-containing short double-stranded RNAs or with a deoxy-inosine-modified ssRNA. Inosine-mediated increase of self-secondary structure of an ssRNA resulted in potentiated IFN-α production in human PBMCs through TLR7 recruitment, as established through the use of a TLR7 antagonist and Tlr7-deficient cells. There was a correlation between hyperediting of influenza A viral ssRNA and its ability to stimulate TNF-α, independent of 5'-triphosphate residues, and involving Adar-1. Furthermore, A-to-I editing of viral ssRNA directly enhanced mouse Tlr7 sensing, when present in proportions reproducing biologically relevant levels of RNA editing. Thus, we demonstrate for the first time that inosine incorporation into immunostimulatory ssRNA can potentiate TLR7/8 activation. Our results suggest a novel function of A-to-I RNA editing, which is to facilitate TLR7/8 sensing of phagocytosed viral RNA.
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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.