ArticleGastroenterology2017
Tumor Necrosis Factor Inhibits Spread of Hepatitis C Virus Among Liver Cells, Independent From Interferons.
Article in Gastroenterology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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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
16 citing papers in PubMed, 26 citations in OpenAlex.
- Integrated Multi-Omics Analysis Reveals Cytokine Network Dynamics and Prognostic Signatures in Hepatitis B Virus-Associated Hepatocellular Carcinoma.Applied biochemistry and biotechnology · 2026Article
- Exosomal microRNAs as biomarkers for viral replication in tofacitinib-treated rheumatoid arthritis patients with hepatitis C.Scientific reports · 2024Article
- USP18 enhances dengue virus replication by regulating mitochondrial DNA release.Scientific reports · 2023Article
- Circadian control of ConA-induced acute liver injury and inflammatory response via Bmal1 regulation of Junb.JHEP reports : innovation in hepatology · 2023Article
- TNFR2 is a potent prognostic biomarker for post-transplant lung metastasis in patients with hepatocellular carcinoma.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2023Article
- Enhanced TLR3 responsiveness in hepatitis C virus resistant women from the Irish anti-D cohort.Cell reports. Medicine · 2022Article
- 17β-Oestradiol Protects from Hepatitis C Virus Infection through Induction of Type I Interferon.Viruses · 2022Article
- TNFα-induced metabolic reprogramming drives an intrinsic anti-viral state.PLoS pathogens · 2022Article
- HIV-1-Mediated Acceleration of Oncovirus-Related Non-AIDS-Defining Cancers.Biomedicines · 2022Review
- Glycometabolism regulates hepatitis C virus release.PLoS pathogens · 2021Article
- Promising Roles of Exosomal microRNAs in Systemic Lupus Erythematosus.Frontiers in immunology · 2021Review
- Identification of Hub genes associated with infection of three lung cell lines by SARS-CoV-2 with integrated bioinformatics analysis.Journal of cellular and molecular medicine · 2020Article
- Article
- MAIT cells and viruses.Immunology and cell biology · 2018Review
- The association between TNFR gene polymorphisms and the risk of Hepatitis B Virus-Related Liver Diseases in Chinese population.Scientific reports · 2018Article
- Turning the tables on cytomegalovirus: targeting viral Fc receptors by CARs containing mutated CH2-CH3 IgG spacer domains.Journal of translational medicine · 2018Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsTumor necrosis factor (TNF) is an inflammatory cytokine expressed by human fetal liver cells (HFLCs) after infection with cell culture-derived hepatitis C virus (HCV). TNF has been reported to increase entry of HCV pseudoparticles into hepatoma cells and inhibit signaling by interferon alpha (IFNα), but have no effect on HCV-RNA replication. We investigated the effects of TNF on HCV infection of and spread among Huh-7 hepatoma cells and primary HFLCs.
methodsHuman hepatoma (Huh-7 and Huh-7.5) and primary HFLCs were incubated with TNF and/or recombinant IFNA2A, IFNB, IFNL1, and IFNL2 before or during HCV infection. We used 2 fully infectious HCV chimeric viruses of genotype 2A in these studies: J6/JFH (clone 2) and Jc1(p7-nsGluc2A) (Jc1G), which encodes a secreted luciferase reporter. We measured HCV replication, entry, spread, production, and release in hepatoma cells and HFLCs.
resultsTNF inhibited completion of the HCV infectious cycle in hepatoma cells and HFLCs in a dose-dependent and time-dependent manner. This inhibition required TNF binding to its receptor. Inhibition was independent of IFNα, IFNβ, IFNL1, IFNL2, or Janus kinase signaling via signal transducer and activator of transcription. TNF reduced production of infectious viral particles by Huh-7 and HFLC, and thereby reduced the number of infected cells and focus size. TNF had little effect on HCV replicons and increased entry of HCV pseudoparticles. When cells were incubated with TNF before infection, the subsequent antiviral effects of IFNs were increased.
conclusionsIn a cell culture system, we found TNF to have antiviral effects independently of, as well as in combination with, IFNs. TNF inhibits HCV infection despite increased HCV envelope glycoprotein-mediated infection of liver cells. These findings contradict those from other studies, which have reported that TNF blocks signal transduction in response to IFNs. The destructive inflammatory effects of TNF must be considered along with its antiviral effects.
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