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http://purl.uniprot.org/citations/23469178http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/23469178http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/23469178http://www.w3.org/2000/01/rdf-schema#comment"The lack of small animal models for hepatitis C virus has impeded the discovery and development of anti-HCV drugs. HCV-IRES plays an important role in HCV gene expression, and is an attractive target for antiviral therapy. In this study, we report a zebrafish model with a biscistron expression construct that can co-transcribe GFP and HCV-core genes by human hepatic lipase promoter and zebrafish liver fatty acid binding protein enhancer. HCV core translation was designed mediated by HCV-IRES sequence and gfp was by a canonical cap-dependent mechanism. Results of fluorescence image and in situ hybridization indicate that expression of HCV core and GFP is liver-specific; RT-PCR and Western blotting show that both core and gfp expression are elevated in a time-dependent manner for both transcription and translation. It means that the HCV-IRES exerted its role in this zebrafish model. Furthermore, the liver-pathological impact associated with HCV-infection was detected by examination of gene markers and some of them were elevated, such as adiponectin receptor, heparanase, TGF-β, PDGF-α, etc. The model was used to evaluate three clinical drugs, ribavirin, IFNα-2b and vitamin B12. The results show that vitamin B12 inhibited core expression in mRNA and protein levels in dose-dependent manner, but failed to impact gfp expression. Also VB12 down-regulated some gene transcriptions involved in fat liver, liver fibrosis and HCV-associated pathological process in the larvae. It reveals that HCV-IRES responds to vitamin B12 sensitively in the zebrafish model. Ribavirin did not disturb core expression, hinting that HCV-IRES is not a target site of ribavirin. IFNα-2b was not active, which maybe resulted from its degradation in vivo for the long time. These findings demonstrate the feasibility of the zebrafish model for screening of anti-HCV drugs targeting to HCV-IRES. The zebrafish system provides a novel evidence of using zebrafish as a HCV model organism."xsd:string
http://purl.uniprot.org/citations/23469178http://purl.org/dc/terms/identifier"doi:10.1371/journal.pone.0056985"xsd:string
http://purl.uniprot.org/citations/23469178http://purl.uniprot.org/core/author"Zhang J.P."xsd:string
http://purl.uniprot.org/citations/23469178http://purl.uniprot.org/core/author"Zhang J.P."xsd:string
http://purl.uniprot.org/citations/23469178http://purl.uniprot.org/core/author"Zhao Y."xsd:string
http://purl.uniprot.org/citations/23469178http://purl.uniprot.org/core/author"Zhao Y."xsd:string
http://purl.uniprot.org/citations/23469178http://purl.uniprot.org/core/author"Zhao L.X."xsd:string
http://purl.uniprot.org/citations/23469178http://purl.uniprot.org/core/author"Zhao L.X."xsd:string
http://purl.uniprot.org/citations/23469178http://purl.uniprot.org/core/author"Qin W."xsd:string
http://purl.uniprot.org/citations/23469178http://purl.uniprot.org/core/author"Qin W."xsd:string
http://purl.uniprot.org/citations/23469178http://purl.uniprot.org/core/author"Jiang J.D."xsd:string
http://purl.uniprot.org/citations/23469178http://purl.uniprot.org/core/author"Jiang J.D."xsd:string
http://purl.uniprot.org/citations/23469178http://purl.uniprot.org/core/author"Hu Z.Y."xsd:string
http://purl.uniprot.org/citations/23469178http://purl.uniprot.org/core/author"Hu Z.Y."xsd:string
http://purl.uniprot.org/citations/23469178http://purl.uniprot.org/core/author"Peng Z.G."xsd:string
http://purl.uniprot.org/citations/23469178http://purl.uniprot.org/core/author"Peng Z.G."xsd:string
http://purl.uniprot.org/citations/23469178http://purl.uniprot.org/core/author"Song D.Q."xsd:string
http://purl.uniprot.org/citations/23469178http://purl.uniprot.org/core/author"Song D.Q."xsd:string
http://purl.uniprot.org/citations/23469178http://purl.uniprot.org/core/author"Tong J.W."xsd:string
http://purl.uniprot.org/citations/23469178http://purl.uniprot.org/core/author"Tong J.W."xsd:string
http://purl.uniprot.org/citations/23469178http://purl.uniprot.org/core/author"Ding C.B."xsd:string
http://purl.uniprot.org/citations/23469178http://purl.uniprot.org/core/author"Ding C.B."xsd:string
http://purl.uniprot.org/citations/23469178http://purl.uniprot.org/core/date"2013"xsd:gYear