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Mol Cell. 2012 Oct 26;48(2):313-21. doi: 10.1016/j.molcel.2012.07.032. Epub 2012 Sep 6.

Hepatic expression of HCV RNA-dependent RNA polymerase triggers innate immune signaling and cytokine production.

Author information

1
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

Abstract

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.

PMID:
22959272
PMCID:
PMC3483424
DOI:
10.1016/j.molcel.2012.07.032
[Indexed for MEDLINE]
Free PMC Article

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