ArticleThe Journal of biological chemistry2012
Epigenetic regulation of tumor necrosis factor α (TNFα) release in human macrophages by HIV-1 single-stranded RNA (ssRNA) is dependent on TLR8 signaling.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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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.
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Who cites it
30 citing papers in PubMed, 47 citations in OpenAlex.
- p53-responsive TLR8 SNP enhances human innate immune response to respiratory syncytial virus.The Journal of clinical investigation · 2019Trial
- Dynamic regulatory mechanism of cholesterol 25-hydroxylase-mediated antiviral response in RNA virus infections.Frontiers in cellular and infection microbiology · 2026Review
- IL-8/CD181 Mediated Inflammation in SLE-Associated Hemolytic Anemia.Iranian journal of pathology · 2025Article
- Generation of porcine PK-15 cells lacking the Ifnar1 or Stat2 gene to optimize the efficiency of viral isolation.PloS one · 2023Article
- Association of Plasma Eicosanoid Levels With Immune, Viral, and Cognitive Outcomes in People With HIV.Neurology · 2022Article
- Enterovirus 71 3C proteolytically processes the histone H3 N-terminal tail during infection.Virologica Sinica · 2022Article
- Nafamostat reduces systemic inflammation in TLR7-mediated virus-like illness.Journal of neuroinflammation · 2022Article
- Host Defence RNases as Antiviral Agents against Enveloped Single Stranded RNA Viruses.Virulence · 2021Review
- Unlocking the complexity of HIV and Mycobacterium tuberculosis coinfection.The Journal of clinical investigation · 2021Article
- Sequence-specific extracellular microRNAs activate TLR7 and induce cytokine secretion and leukocyte migration.Molecular and cellular biochemistry · 2021Article
- Toll-like receptor-mediated innate immunity against herpesviridae infection: a current perspective on viral infection signaling pathways.Virology journal · 2020Review
- Maternal exposure to soy diet reduces atheroma in hyperlipidemic F1 offspring mice by promoting macrophage and T cell anti-inflammatory responses.Atherosclerosis · 2020Article
- Immunomodulatory Effects of Hydroxychloroquine and Chloroquine in Viral Infections and Their Potential Application in Retinal Gene Therapy.International journal of molecular sciences · 2020Review
- Extracellular RNAs in periodontopathogenic outer membrane vesicles promote TNF-α production in human macrophages and cross the blood-brain barrier in mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Cystathionine-γ-lyase ameliorates the histone demethylase JMJD3-mediated autoimmune response in rheumatoid arthritis.Cellular & molecular immunology · 2019Article
- Simian Immunodeficiency Virus Targeting of CXCR3Journal of virology · 2017Article
- Circulating and Exosome-Packaged Hepatitis C Single-Stranded RNA Induce Monocyte Differentiation via TLR7/8 to Polarized Macrophages and Fibrocytes.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Coexpression Analysis of Transcriptome on AIDS and Other Human Disease Pathways by Canonical Correlation Analysis.International journal of genomics · 2017Article
- The therapeutic potential of epigenetic manipulation during infectious diseases.Pharmacology & therapeutics · 2016Review
- Innate immune reconstitution with suppression of HIV-1.JCI insight · 2016Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Human macrophages at mucosal sites are essential targets for acute HIV infection. During the chronic phase of infection, they are persistent reservoirs for the AIDS virus. HIV virions gain entry into macrophages following ligation of surface CD4-CCR5 co-receptors, which leads to the release of two copies of HIV ssRNA. These events lead to reverse transcription and viral replication initiation. Toll-like receptors TLR7 and TLR8 recognize specific intracellular viral ssRNA sequences, but in human alveolar macrophages, their individual roles in TLR-mediated HIV ssRNA recognition are unclear. In the current study, HIV-1 ssRNA induced TNFα release in a dose-dependent manner in adherent human macrophages expressing both intracellular TLR7 and TLR8. This response was reduced by inhibiting either endocytosis (50 μm dynasore) or endosomal acidification (1 μg/ml chloroquine). Either MYD88 or TLR8 gene knockdown with relevant siRNA reduced HIV-1 ssRNA-mediated TNFα release, but silencing TLR7 had no effect on this response. Furthermore, HIV-1 ssRNA induced histone 4 acetylation at the TNFα promoter as well as trimethylation of histone 3 at lysine 4, whereas TLR8 gene knockdown reduced these effects. Taken together in human macrophages, TLR8 binds and internalizes HIV ssRNA, leading to endosomal acidification, chromatin remodeling, and increases in TNFα release. Drugs targeting macrophage TLR8-linked signaling pathways may modulate the innate immune response to acute HIV infection by reducing viral replication.
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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.