ArticleJournal of virology2014
Direct, interferon-independent activation of the CXCL10 promoter by NF-κB and interferon regulatory factor 3 during hepatitis C virus infection.
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 85 papers.
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Who cites it
85 citing papers in PubMed, 126 citations in OpenAlex.
- Regulatory polymorphism of CXCL10 rs1439490 in seronegative occult hepatitis C virus infection.World journal of gastroenterology · 2018Trial
- Intrahepatic and Peripheral CXCL10 Expression in Hepatitis C Virus-Infected Patients Treated With Telaprevir, Pegylated Interferon, and Ribavirin.The Journal of infectious diseases · 2015Trial
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- Codon Optimality Modulates Cellular Stress and Innate Immune Responses Triggered by Exogenous RNAs.Journal of molecular biology · 2026Article
- Neonatal Inflammatory Profiles Associated With Perinatally Acquired Hepatitis C Viral Infection.The Pediatric infectious disease journal · 2026Article
- LncRNA AFAP1-AS1 mediates therapy-dependent expression of CCL5, CXCL10 and MMP9 in multiple sclerosis.Biochemistry and biophysics reports · 2026Article
- Dissection of innate-immune-ligand- and interferon-protein-mediated transcriptional responses in human THP1 cell states.Communications biology · 2026Article
- Endothelial IRE1 signaling maintains blood-brain barrier integrity and limits neuroinflammation after traumatic brain injury.Cell death & disease · 2026Article
- A Subset of Pro-inflammatory CXCL10+ LILRB2+ Macrophages Derives From Recipient Monocytes and Drives Renal Allograft Rejection.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Transcriptomic profiling reveals selective attenuation of interferon-associated inflammatory signaling and induction of metallothioneins by a zinc-containing oral rinse.Frontiers in immunology · 2026Article
- Xylosyltransferase-II deficiency rewires innate immune signaling and destabilizes polarization in human macrophages.Frontiers in immunology · 2026Article
- Pollutant particle priming amplifies airway compartment specific neutrophil and macrophage inflammatory programs following house dust mite acute exposure.Frontiers in immunology · 2026Article
- Double stranded RNA sensing is silenced during early embryonic development.Nature communications · 2025Article
- Distinct inflammatory imprint in non-cirrhotic and cirrhotic patients before and after direct-acting antiviral therapy.Clinical and molecular hepatology · 2025Article
- The role of liver macrophages in viral liver pathogenesis.Journal of leukocyte biology · 2025Review
- Perforin-2 is overexpressed in Kikuchi-Fujimoto disease.Virchows Archiv : an international journal of pathology · 2025Article
- Sustained Accumulation of Molecular Clock Suppressors Period 1 and Period 2 Promotes C2C12 Myotube Atrophy Through an Autocrine-Mediated Mechanism With Relevance to Androgen Deprivation-Induced Limb Muscle Mass Loss.Function (Oxford, England) · 2025Article
- Molecular features of TNBC govern heterogeneity in the response to radiation and autophagy inhibition.Cell death & disease · 2025Article
- Plasmacytoid dendritic cell sensing of hepatitis E virus is shaped by both viral and host factors.Life science alliance · 2025Article
- Poly(I:C) signaling induces robust CXCL10 production and apoptosis in human esophageal squamous cell carcinoma cells.Human cell · 2025Article
25 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Hepatitis C virus (HCV) infection of hepatocytes leads to transcriptional induction of the chemokine CXCL10, which is considered an interferon (IFN)-stimulated gene. However, we have recently shown that IFNs are not required for CXCL10 induction in hepatocytes during acute HCV infection. Since the CXCL10 promoter contains binding sites for several proinflammatory transcription factors, we investigated the contribution of these factors to CXCL10 transcriptional induction during HCV infection in vitro. Wild-type and mutant CXCL10 promoter-luciferase reporter constructs were used to identify critical sites of transcriptional regulation. The proximal IFN-stimulated response element (ISRE) and NF-κB binding sites positively regulated CXCL10 transcription during HCV infection as well as following exposure to poly(I·C) (a Toll-like receptor 3 [TLR3] stimulus) and 5' poly(U) HCV RNA (a retinoic acid-inducible gene I [RIG-I] stimulus) from two viral genotypes. Conversely, binding sites for AP-1 and CCAAT/enhancer-binding protein β (C/EBP-β) negatively regulated CXCL10 induction in response to TLR3 and RIG-I stimuli, while only C/EBP-β negatively regulated CXCL10 during HCV infection. We also demonstrated that interferon-regulatory factor 3 (IRF3) is transiently recruited to the proximal ISRE during HCV infection and localizes to the nucleus in HCV-infected primary human hepatocytes. Furthermore, IRF3 activated the CXCL10 promoter independently of type I or type III IFN signaling. The data indicate that sensing of HCV infection by RIG-I and TLR3 leads to direct recruitment of NF-κB and IRF3 to the CXCL10 promoter. Our study expands upon current knowledge regarding the mechanisms of CXCL10 induction in hepatocytes and lays the foundation for additional mechanistic studies that further elucidate the combinatorial and synergistic aspects of immune signaling pathways.
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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.