Double-stranded RNA-induced interferon-beta and inflammatory cytokine production modulated by hepatitis C virus serine proteases derived from patients with hepatic diseases

Hiromichi Dansako, Masanori Ikeda, Yasuo Ariumi, Takaji Wakita, Nobuyuki Kato

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

We previously demonstrated that hepatitis C virus (HCV) serine protease NS3-4A was unable to cleave TRIF (adaptor protein of Toll-like receptor 3), resulting in a lack of suppression of the TRIF-mediated pathway, whereas NS3-4A cleaved Cardif (adaptor protein of retinoic acid-inducible gene I or melanoma differentiation-associated gene-5), resulting in an interruption of the Cardif-mediated pathway in non-neoplastic human hepatocyte PH5CH8 cells. To elucidate these observations, we examined the cleavage potential of NS3-4A for TRIF in PH5CH8 cells, genome-length HCV RNA-replicating O cells, and HCV-infected cells, and we demonstrated that NS3-4A lacked the ability to cleave endogenous TRIF, regardless of HCV strains derived from patients with different stages of hepatic disease. Furthermore, we demonstrated that inflammatory cytokine production by NF-κB activation via the TRIF-mediated pathway also remained unsuppressed by NS3-4A. These results suggest that the inhibitory effects of NS3-4A on antiviral signaling pathways are limited to the Cardif-mediated pathway in human hepatocytes.

Original languageEnglish
Pages (from-to)801-810
Number of pages10
JournalArchives of Virology
Volume154
Issue number5
DOIs
Publication statusPublished - May 1 2009

ASJC Scopus subject areas

  • Virology

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