bile acids specifically increase hepatitis c virus rna-replication胆汁酸专门增加丙型肝炎病毒rna复制.pdfVIP

bile acids specifically increase hepatitis c virus rna-replication胆汁酸专门增加丙型肝炎病毒rna复制.pdf

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bile acids specifically increase hepatitis c virus rna-replication胆汁酸专门增加丙型肝炎病毒rna复制

Bile Acids Specifically Increase Hepatitis C Virus RNA- Replication 1 1 1 1 2 Patrick Chhatwal , Dorothea Bankwitz , Juliane Gentzsch , Anne Frentzen , Philipp Schult , 2 1 Volker Lohmann , Thomas Pietschmann * 1 Department of Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research; a joint venture between the Medical School Hannover and the Helmholtz Centre for Infection Research, Hannover, Germany, 2 Department of Infectious Diseases, Molecular Virology, University of Heidelberg, Heidelberg, Germany Abstract Background: Hepatitis C virus (HCV) patients with high serum levels of bile acids (BAs) respond poorly to IFN therapy. BAs have been shown to increase RNA-replication of genotype 1 but not genotype 2a replicons. Since BAs modulate lipid metabolism including lipoprotein secretion and as HCV depends on lipids and lipoproteins during RNA-replication, virus production and cell entry, BAs may affect multiple steps of the HCV life cycle. Therefore, we analyzed the influence of BAs on individual steps of virus replication. Methods: We measured replication of subgenomic genotype (GT) 1b and 2a RNAs as well as full-length GT2a genomes in the presence of BAs using quantitative RT-PCR and luciferase assays. Cell entry was determined using HCV pseudoparticles (HCVpp). Virus assembly and release were quantified using a core-specific ELISA. Replicon chimeras were employed to characterize genotype-specific modulation of HCV by BAs. Lunet CD81/GFP-NLS-MAVS cells were used to determine in

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