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


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2009-05

AUTHORS

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

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-kappaB 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. More... »

PAGES

801-810

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00705-009-0375-z

DOI

http://dx.doi.org/10.1007/s00705-009-0375-z

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1033649276

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/19353241


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