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Lipid Droplet Isolation for Quantitative Mass Spectrometry Analysis
10:23

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Published on: April 17, 2017

Bile acids specifically increase hepatitis C virus RNA-replication.

Patrick Chhatwal1, Dorothea Bankwitz, Juliane Gentzsch

  • 1Department of Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research; a joint venture between Medical School Hannover and Helmholtz Centre for Infection Research, Hannover, Germany.

Plos One
|May 5, 2012
PubMed
Summary
This summary is machine-generated.

Bile acids enhance Hepatitis C virus (HCV) RNA replication, particularly for genotype 1b and certain genotype 2a variants. This finding may impact antiviral treatment efficacy in patients with high bile acid levels.

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Area of Science:

  • Hepatology and Virology
  • Molecular Biology
  • Viral Pathogenesis

Background:

  • High serum bile acids (BAs) correlate with poor response to interferon therapy in Hepatitis C virus (HCV) patients.
  • Bile acids are known to influence lipid metabolism, a process crucial for HCV replication, assembly, and entry.

Purpose of the Study:

  • To investigate the specific effects of bile acids on individual steps of the HCV life cycle.
  • To determine how bile acids influence RNA replication across different HCV genotypes.

Main Methods:

  • Quantitative RT-PCR and luciferase assays were used to measure RNA replication of genotype 1b and 2a replicons and full-length genomes.
  • HCV pseudoparticles were used to assess cell entry, and core-specific ELISA quantified virus assembly and release.
  • Replicon chimeras and specific cell lines were employed to analyze genotype-specific modulation and infection.

Main Results:

  • Bile acids significantly increased RNA replication of genotype 1b replicons (up to 10-fold) but not subgenomic genotype 2a replicons.
  • No significant effect of bile acids was observed on viral RNA translation, assembly, release, or cell entry.
  • Full-length genotype 1b and 2a genomes, as well as low-replication genotype 2a replicons, showed enhanced replication in the presence of bile acids.

Conclusions:

  • Bile acids specifically enhance HCV RNA replication, affecting both genotype 1 and certain genotype 2a variants.
  • This enhancement is observed for full-length genomes and replicons with reduced replication capacity.
  • The stimulatory effect of bile acids on HCV replication could influence the effectiveness of antiviral therapies and aid in cell culture replication of primary viral isolates.