Document Detail


Hepatic expression of HCV RNA-dependent RNA polymerase triggers innate immune signaling and cytokine production.
MedLine Citation:
PMID:  22959272     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-09-06
Journal Detail:
Title:  Molecular cell     Volume:  48     ISSN:  1097-4164     ISO Abbreviation:  Mol. Cell     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-29     Completed Date:  2013-04-03     Revised Date:  2013-11-05    
Medline Journal Info:
Nlm Unique ID:  9802571     Medline TA:  Mol Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  313-21     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Affiliation:
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
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MeSH Terms
Descriptor/Qualifier:
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:
CA118165/CA/NCI NIH HHS; P42ES010337/ES/NIEHS NIH HHS; R01 CA118165/CA/NCI NIH HHS; WT086755//Wellcome Trust
Chemical
Reg. No./Substance:
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:
Hepatology. 2013 Mar;57(3):1275-7   [PMID:  23426794 ]

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