Journal ArticleDOI
Hepatitis C virus (HCV) NS2 protein up-regulates HCV IRES-dependent translation and down-regulates NS5B RdRp activity
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TLDR
Results showed that HCV NS2 protein up-regulated HCV IRES-dependent translation in a specific and dose-dependent manner in Huh7 cells but not in HeLa and HepG2 cells, and NS2protein inhibited NS5B RdRp activity in a dose-independent manner in all three cell lines.Abstract:
Chronic hepatitis C virus (HCV) infection often leads to liver cancer. The HCV NS2 protein is a hydrophobic transmembrane protein that associates with several cellular proteins in mammalian cells. In this report, we investigated the function of NS2 protein on HCV replication and translation by using a transient cell-based expression system. Cells co-transfected with pcDNA3.1 (-)-NS2 and the dual-luciferase reporter construct containing the HCV IRES were used to detect the effect of NS2 protein on HCV translation. Cells co-transfected with pcDNA3.1(-)-NS2, pcDNA-NS5B and a reporter plasmid were used to detect the effect of NS2 protein on HCV replication. The results showed that HCV NS2 protein up-regulated HCV IRES-dependent translation in a specific and dose-dependent manner in Huh7 cells but not in HeLa and HepG2 cells, and NS2 protein inhibited NS5B RdRp activity in a dose-independent manner in all three cell lines. These findings may suggest a novel mechanism by which HCV modulates its NS5B replication and IRES-dependent translation and facilitates virus persistence.read more
Citations
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(−)-Epigallocatechin-3-gallate inhibits the replication cycle of hepatitis C virus
TL;DR: It is found that hepatitis C virus (HCV) infection was significantly suppressed by EGCG in an HCV cell culture system using a JFH1-GFP chimeric virus, with a 50 % effective concentration (EC50) of 17.9 μM.
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DNA methyltransferases 1 and 3B are required for hepatitis C virus infection in cell culture
TL;DR: In this paper, the authors identified DNMT1 and DNMT3B as host factors involved in hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC) propagation.
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Chapter 20 Progress towards the Discovery and Development of Specifically Targeted Inhibitors of Hepatitis C Virus
TL;DR: With compounds acting at multiple sites in the virus replication cycle in development, there is reason to be optimistic about the potential to identify effective combinations that offer higher rates of therapeutic cure of HCV infection resistant to the current SOC.
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Serum cystatin C correlates negatively with viral load in treatment-naïve children with chronic hepatitis C.
Behairy E. Behairy,Magdy A. Saber,Ibrahim A Elhenawy,Sahar S. Abou-Zeinah,Ahmed A. El-Sharawy,Mostafa Mohamed Sira +5 more
TL;DR: Investigation of the relation between serum levels of cystatin C and HCV viremia in treatment-naïve children with chronic hepatitis C found an inhibitory effect of cy statin C on HCV replication through inhibiting its NS2/3 and tempting for further studies for cyStatin C as a possible adjuvant therapy for HCV infection.
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Novel nucleotide and amino acid covariation between the 5'UTR and the NS2/NS3 proteins of hepatitis C virus: bioinformatic and functional analyses.
Hung Yu Sun,Nai Ying Ou,Shainn Wei Wang,Wen-Chun Liu,Ting Fang Cheng,Shiou Jiuan Shr,Koun Tem Sun,Ting-Tsung Chang,Kung Chia Young +8 more
TL;DR: 5′UTR243 co-varies with specific NS2/3 protein amino acid residues, which may have significant structural and functional consequences for HCV replication and possibly can be exploited in the development of advanced anti-HCV medication.
References
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TL;DR: Experimental evidence that an RNA‐dependent RNA polymerase is encoded by HCV and that this enzymatic activity is the function of the 65 kDa non‐structural protein 5B (NS5B) is presented, representing a first important step towards a better understanding of the life cycle of the HCV.
Journal ArticleDOI
Hepatitis C Virus-Encoded Enzymatic Activities and Conserved RNA Elements in the 3′ Nontranslated Region Are Essential for Virus Replication In Vivo
TL;DR: Data suggest that these four HCV-encoded enzymatic activities and the conserved 3′ terminal RNA element are essential for productive replication in vivo.