Toll-like receptor 3 mediates establishment of an antiviral state against hepatitis C virus in hepatoma cells
| Autor: | Jie Wang, Stanley M. Lemon, Yuqiong Liang, Kui Li, Nan Wang, Santhana G. T. Devaraj |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Carcinoma
Hepatocellular Hepatitis C virus viruses Immunology Cellular Response to Infection Hepacivirus Biology medicine.disease_cause Microbiology Antiviral Agents Models Biological Virus Proinflammatory cytokine DEAD-box RNA Helicases Virology Cell Line Tumor Chlorocebus aethiops medicine Animals Humans Receptors Immunologic Vero Cells RNA Double-Stranded Toll-like receptor Microscopy Confocal virus diseases Toll-Like Receptor 3 Phenotype TRIF Insect Science TLR3 DEAD Box Protein 58 Signal transduction Interferon regulatory factors Signal Transduction |
| Zdroj: | Journal of virology. 83(19) |
| ISSN: | 1098-5514 |
| Popis: | Toll-like receptor-3 (TLR3) senses double-stranded RNA, initiating signaling that activates NF-κB and interferon regulatory factor 3 (IRF-3), thereby inducing the synthesis of proinflammatory cytokines, type I interferons, and numerous interferon-stimulated genes (ISGs). This pathway has not been extensively investigated in human hepatocytes, and its role in sensing and protecting against hepatitis virus infections is uncertain. We show here that primary human hepatocytes express TLR3 and robustly upregulate ISGs upon poly(I·C) stimulation. We also show that TLR3 senses hepatitis C virus (HCV) infection when expressed in permissive hepatoma cells, acting independently of retinoic acid-inducible gene I and inducing IRF-3 activation and the synthesis of ISGs that restrict virus replication. In turn, HCV infection reduces the abundance of TRIF, an essential TLR3 adaptor, and impairs poly(I·C)-induced signaling. The induction and disruption of TLR3 signaling by HCV may be important factors in determining the outcome of infection and the ability of HCV to establish persistent infections. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|