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Inhibition of hepatitis C virus translation and subgenomic replication by siRNAs directed against highly conserved HCV sequence and cellular HCV cofactors

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Inhibition of hepatitis C virus translation and subgenomic replication by siRNAs directed against highly conserved HCV sequence and cellular HCV cofactors. / Korf, Mortimer; Jarczak, Dominik; Beger, Carmela; Manns, Michael P; Krüger, Martin.

in: J HEPATOL, Jahrgang 43, Nr. 2, 08.2005, S. 225-34.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Korf, M, Jarczak, D, Beger, C, Manns, MP & Krüger, M 2005, 'Inhibition of hepatitis C virus translation and subgenomic replication by siRNAs directed against highly conserved HCV sequence and cellular HCV cofactors', J HEPATOL, Jg. 43, Nr. 2, S. 225-34. https://doi.org/10.1016/j.jhep.2005.02.046

APA

Korf, M., Jarczak, D., Beger, C., Manns, M. P., & Krüger, M. (2005). Inhibition of hepatitis C virus translation and subgenomic replication by siRNAs directed against highly conserved HCV sequence and cellular HCV cofactors. J HEPATOL, 43(2), 225-34. https://doi.org/10.1016/j.jhep.2005.02.046

Vancouver

Korf M, Jarczak D, Beger C, Manns MP, Krüger M. Inhibition of hepatitis C virus translation and subgenomic replication by siRNAs directed against highly conserved HCV sequence and cellular HCV cofactors. J HEPATOL. 2005 Aug;43(2):225-34. https://doi.org/10.1016/j.jhep.2005.02.046

Bibtex

@article{48e210be2abe4e16b0ebf179114feb0b,
title = "Inhibition of hepatitis C virus translation and subgenomic replication by siRNAs directed against highly conserved HCV sequence and cellular HCV cofactors",
abstract = "BACKGROUND/AIMS: Small interfering RNAs (siRNAs) are an efficient tool to specifically inhibit gene expression by RNA interference. Since hepatitis C virus (HCV) replicates in the cytoplasm of liver cells without integration into the host genome, RNA-directed antiviral strategies are likely to successfully block the HCV replication cycle. Additional benefit might arise from inhibition of cellular cofactors of HCV replication, such as proteasome alpha-subunit 7 (PSMA7) or Hu antigen R (HuR).METHODS: In this study, we investigated direct and cofactor-mediated inhibition of HCV by a panel of DNA-based retroviral vectors expressing siRNAs against highly conserved HCV sequences or the putative HCV cofactors PSMA7 and HuR. Effects were determined in HCV IRES-mediated translation assays and subgenomic HCV replicon cells.RESULTS: PSMA7- and HuR-directed siRNAs successfully inhibited expression of the endogenous genes, and PSMA7 and HuR silencing significantly diminished HCV replicon RNA and NS5B protein levels. HCV-directed siRNAs substantially inhibited HCV IRES-mediated translation and subgenomic HCV replication. Combinations of PSMA7- and HuR-directed siRNAs with HCV-directed siRNAs revealed additive HCV RNA inhibitory effects in monocistronic replicon cells.CONCLUSIONS: A dual approach of direct- and cofactor-mediated inhibition of HCV replication might avoid selection of mutants and thereby become a powerful strategy against HCV.",
keywords = "Antigens, Surface, Blotting, Northern, Blotting, Western, Cysteine Endopeptidases, ELAV Proteins, ELAV-Like Protein 1, Gene Expression Regulation, Viral, Genes, Viral, Genome, Viral, Hepacivirus, Humans, In Vitro Techniques, Liver, Plasmids, Proteasome Endopeptidase Complex, Protein Biosynthesis, Protein Subunits, RNA, Small Interfering, RNA, Viral, RNA-Binding Proteins, Transfection, Viral Nonstructural Proteins, Viral Structural Proteins, Virus Replication",
author = "Mortimer Korf and Dominik Jarczak and Carmela Beger and Manns, {Michael P} and Martin Kr{\"u}ger",
year = "2005",
month = aug,
doi = "10.1016/j.jhep.2005.02.046",
language = "English",
volume = "43",
pages = "225--34",
journal = "J HEPATOL",
issn = "0168-8278",
publisher = "Elsevier",
number = "2",

}

RIS

TY - JOUR

T1 - Inhibition of hepatitis C virus translation and subgenomic replication by siRNAs directed against highly conserved HCV sequence and cellular HCV cofactors

AU - Korf, Mortimer

AU - Jarczak, Dominik

AU - Beger, Carmela

AU - Manns, Michael P

AU - Krüger, Martin

PY - 2005/8

Y1 - 2005/8

N2 - BACKGROUND/AIMS: Small interfering RNAs (siRNAs) are an efficient tool to specifically inhibit gene expression by RNA interference. Since hepatitis C virus (HCV) replicates in the cytoplasm of liver cells without integration into the host genome, RNA-directed antiviral strategies are likely to successfully block the HCV replication cycle. Additional benefit might arise from inhibition of cellular cofactors of HCV replication, such as proteasome alpha-subunit 7 (PSMA7) or Hu antigen R (HuR).METHODS: In this study, we investigated direct and cofactor-mediated inhibition of HCV by a panel of DNA-based retroviral vectors expressing siRNAs against highly conserved HCV sequences or the putative HCV cofactors PSMA7 and HuR. Effects were determined in HCV IRES-mediated translation assays and subgenomic HCV replicon cells.RESULTS: PSMA7- and HuR-directed siRNAs successfully inhibited expression of the endogenous genes, and PSMA7 and HuR silencing significantly diminished HCV replicon RNA and NS5B protein levels. HCV-directed siRNAs substantially inhibited HCV IRES-mediated translation and subgenomic HCV replication. Combinations of PSMA7- and HuR-directed siRNAs with HCV-directed siRNAs revealed additive HCV RNA inhibitory effects in monocistronic replicon cells.CONCLUSIONS: A dual approach of direct- and cofactor-mediated inhibition of HCV replication might avoid selection of mutants and thereby become a powerful strategy against HCV.

AB - BACKGROUND/AIMS: Small interfering RNAs (siRNAs) are an efficient tool to specifically inhibit gene expression by RNA interference. Since hepatitis C virus (HCV) replicates in the cytoplasm of liver cells without integration into the host genome, RNA-directed antiviral strategies are likely to successfully block the HCV replication cycle. Additional benefit might arise from inhibition of cellular cofactors of HCV replication, such as proteasome alpha-subunit 7 (PSMA7) or Hu antigen R (HuR).METHODS: In this study, we investigated direct and cofactor-mediated inhibition of HCV by a panel of DNA-based retroviral vectors expressing siRNAs against highly conserved HCV sequences or the putative HCV cofactors PSMA7 and HuR. Effects were determined in HCV IRES-mediated translation assays and subgenomic HCV replicon cells.RESULTS: PSMA7- and HuR-directed siRNAs successfully inhibited expression of the endogenous genes, and PSMA7 and HuR silencing significantly diminished HCV replicon RNA and NS5B protein levels. HCV-directed siRNAs substantially inhibited HCV IRES-mediated translation and subgenomic HCV replication. Combinations of PSMA7- and HuR-directed siRNAs with HCV-directed siRNAs revealed additive HCV RNA inhibitory effects in monocistronic replicon cells.CONCLUSIONS: A dual approach of direct- and cofactor-mediated inhibition of HCV replication might avoid selection of mutants and thereby become a powerful strategy against HCV.

KW - Antigens, Surface

KW - Blotting, Northern

KW - Blotting, Western

KW - Cysteine Endopeptidases

KW - ELAV Proteins

KW - ELAV-Like Protein 1

KW - Gene Expression Regulation, Viral

KW - Genes, Viral

KW - Genome, Viral

KW - Hepacivirus

KW - Humans

KW - In Vitro Techniques

KW - Liver

KW - Plasmids

KW - Proteasome Endopeptidase Complex

KW - Protein Biosynthesis

KW - Protein Subunits

KW - RNA, Small Interfering

KW - RNA, Viral

KW - RNA-Binding Proteins

KW - Transfection

KW - Viral Nonstructural Proteins

KW - Viral Structural Proteins

KW - Virus Replication

U2 - 10.1016/j.jhep.2005.02.046

DO - 10.1016/j.jhep.2005.02.046

M3 - SCORING: Journal article

C2 - 15964661

VL - 43

SP - 225

EP - 234

JO - J HEPATOL

JF - J HEPATOL

SN - 0168-8278

IS - 2

ER -