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

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-?B and induce cytokine production, including type I interferons (IFN) and IL-6. NS5B-expression also results in liver damage.

SUBMITTER: Yu GY

PROVIDER: S-EPMC3483424 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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

Yu Guann-Yi GY He Guobin G Li Chia-Yang CY Tang Martin M Grivennikov Sergei S Tsai Wan-Ting WT Wu Ming-Sian MS Hsu Chih-Wen CW Tsai Yu Y Wang Lily Hui-Ching LH Karin Michael M

Molecular cell 20120906 2

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 ...[more]

PMID: 22959272

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