| Hepatic expression of HCV RNA-dependent RNA polymerase triggers innate immune signaling and cytokine production. | |
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MedLine Citation:
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PMID: 22959272 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Innate immunity controls pathogen replication and spread. Yet, certain pathogens, such as Hepatitis C Virus (HCV), escape immune elimination and establish persistent infections that promote chronic inflammation and related diseases. Whereas HCV regulatory proteins that attenuate antiviral responses are known, those that promote inflammation and liver injury remain to be identified. Here, we show that transient expression of HCV RNA-dependent RNA polymerase (RdRp), NS5B, in mouse liver and human hepatocytes results in production of small RNA species that activate innate immune signaling via TBK1-IRF3 and NF-κB and induce cytokine production, including type I interferons (IFN) and IL-6. NS5B-expression also results in liver damage. |
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Authors:
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Guann-Yi Yu; Guobin He; Chia-Yang Li; Martin Tang; Sergei Grivennikov; Wan-Ting Tsai; Ming-Sian Wu; Chih-Wen Hsu; Yu Tsai; Lily Hui-Ching Wang; Michael Karin |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-09-06 |
Journal Detail:
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Title: Molecular cell Volume: 48 ISSN: 1097-4164 ISO Abbreviation: Mol. Cell Publication Date: 2012 Oct |
Date Detail:
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Created Date: 2012-10-29 Completed Date: 2013-04-03 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 9802571 Medline TA: Mol Cell Country: United States |
Other Details:
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Languages: eng Pagination: 313-21 Citation Subset: IM |
Copyright Information:
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Copyright © 2012 Elsevier Inc. All rights reserved. |
Affiliation:
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Laboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, School of Medicine, University of California, San Diego, La Jolla, CA 92093-0723, USA. guannyiy@nhri.org.tw |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Hepacivirus* / genetics, metabolism, pathogenicity Hepatitis C, Chronic* / genetics, metabolism, virology Hepatocytes / metabolism Humans Immunity, Innate* Interferon Regulatory Factor-3 / metabolism Interferon Type I / biosynthesis, metabolism Interleukin-6 / biosynthesis, metabolism Liver* / injuries, metabolism, virology Mice NF-kappa B / metabolism Protein-Serine-Threonine Kinases / metabolism Signal Transduction Viral Nonstructural Proteins* / genetics, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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CA118165/CA/NCI NIH HHS; P42ES010337/ES/NIEHS NIH HHS; R01 CA118165/CA/NCI NIH HHS; WT086755//Wellcome Trust |
| Chemical | |
Reg. No./Substance:
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0/IRF3 protein, human; 0/Interferon Regulatory Factor-3; 0/Interferon Type I; 0/Interleukin-6; 0/NF-kappa B; 0/NS-5 protein, hepatitis C virus; 0/Viral Nonstructural Proteins; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/TBK1 protein, human |
| Comments/Corrections | |
Comment In:
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Hepatology. 2013 Mar;57(3):1275-7
[PMID:
23426794
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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