ArticlePLoS pathogens2015
TNF-α Induced by Hepatitis C Virus via TLR7 and TLR8 in Hepatocytes Supports Interferon Signaling via an Autocrine Mechanism.
Article in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 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.
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Who cites it
48 citing papers in PubMed, 66 citations in OpenAlex.
- From viral epigenetic reprogramming to neuroinflammation: Mechanisms driving neurodegeneration.Journal of neurovirology · 2026Review
- Hepatitis C Virus and Type 2 Diabetes: Mechanisms, Clinical Impact, and Post-DAA Management.Journal of medical virology · 2026Review
- Role of autophagy in antiviral innate immunity.Cellular & molecular biology letters · 2026Review
- PTPN2 Negatively Regulates Macrophage Immune Responses and Cellular Bioenergetics.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Review
- Exploring T-Cell Immunity to Hepatitis C Virus: Insights from Different Vaccine and Antigen Presentation Strategies.Vaccines · 2024Review
- Hepatitis B virus e antigen induces atypical metabolism and differentially regulates programmed cell deaths of macrophages.PLoS pathogens · 2024Article
- Bystander Effects and Profibrotic Interactions in Hepatic Stellate Cells during HIV and HCV Coinfection.Journal of immunology research · 2024Article
- HCV-induced autophagy and innate immunity.Frontiers in immunology · 2024Review
- Study on the mechanism of oral administration of tetrandrine during neoadjuvant chemotherapy for colon cancer.Oncology letters · 2023Article
- 17β-Oestradiol Protects from Hepatitis C Virus Infection through Induction of Type I Interferon.Viruses · 2022Article
- The P2X7R-NLRP3 and AIM2 Inflammasome Platforms Mark the Complexity/Severity of Viral or Metabolic Liver Damage.International journal of molecular sciences · 2022Article
- Toll-like Receptor Response to Hepatitis C Virus Infection: A Recent Overview.International journal of molecular sciences · 2022Review
- Hepatitis C virus and intracellular antiviral response.Current opinion in virology · 2022Review
- Article
- A Squalene-Based Nanoemulsion for Therapeutic Delivery of Resiquimod.Pharmaceutics · 2021Article
- Reciprocal induction of hepatitis C virus replication and stimulation of hepatic profibrogenic cytokine release and cellular viability by YKL-40.Annals of translational medicine · 2021Article
- Molecular pathways in viral hepatitis-associated liver carcinogenesis: An update.World journal of clinical cases · 2021Review
- 2-O-Methylhonokiol Suppresses HCV Replication via TRAF6-Mediated NF-kB Activation.International journal of molecular sciences · 2021Article
- Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Invasion by infectious pathogens can elicit a range of cytokine responses from host cells. These cytokines provide the initial host defense mechanism. In this report, we demonstrate that TNF-α, a pro-inflammatory cytokine, can be induced by hepatitis C virus (HCV) in its host cells in a biphasic manner. The initial induction of TNF-α by HCV was prompt and could be blocked by the antibody directed against the HCV E2 envelope protein and by chemicals that inhibit endocytosis, indicating the specificity of endocytic uptake of HCV in this induction. Further studies indicated that the induction of TNF-α was dependent on toll-like receptors 7 and 8 (TLR7/8) but not on other intracellular pattern recognition receptors. Consistently, siRNA-mediated gene silencing of the downstream effectors in the TLR7/8 signaling pathway including MyD88, IRAK1, TRAF6, TAK1 and p65 NF-κB suppressed the expression of TNF-α. The role of p65 NF-κB in the induction of TNF-α via transcriptional up-regulation was further confirmed by the chromatin immunoprecipitation assay. TNF-α induced by HCV could activate its own receptor TNFR1 on hepatocytes to suppress HCV replication. This suppressive effect of TNF-α on HCV was due to its role in supporting interferon signaling, as the suppression of its expression led to the loss of IFNAR2 and impaired interferon signaling and the induction of interferon-stimulated genes. In conclusion, our results indicate that hepatocytes can sense HCV infection via TLR7/8 to induce the expression of TNF-α, which inhibits HCV replication via an autocrine mechanism to support interferon signaling.
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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.