PUBLICATION

Zebrafish as a potential model organism for drug test against hepatitis C virus

Authors
Ding, C.B., Zhang, J.P., Zhao, Y., Peng, Z.G., Song, D.Q., and Jiang, J.D.
ID
ZDB-PUB-110823-26
Date
2011
Source
PLoS One   6(8): e22921 (Journal)
Registered Authors
Ding, Cunbao, Zhang, Jing-pu
Keywords
none
MeSH Terms
  • Antiviral Agents/pharmacology*
  • Hepacivirus/drug effects*
  • Hepacivirus/genetics
  • Hepacivirus/metabolism
  • Replicon/genetics
  • Animals
  • Microinjections
  • Green Fluorescent Proteins/genetics
  • Green Fluorescent Proteins/metabolism
  • In Situ Hybridization
  • Viral Nonstructural Proteins/genetics
  • Viral Nonstructural Proteins/metabolism
  • Larva/genetics
  • Larva/metabolism
  • Larva/virology
  • Hepatocytes/drug effects
  • Hepatocytes/metabolism
  • Hepatocytes/virology
  • Drug Evaluation, Preclinical/methods*
  • Microscopy, Fluorescence
  • Genetic Vectors/administration & dosage
  • Genetic Vectors/genetics
  • Ribavirin/pharmacology
  • Humans
  • Quinolizines/pharmacology
  • Hepatitis C/genetics
  • Hepatitis C/metabolism
  • Hepatitis C/prevention & control
  • Alkaloids/pharmacology
  • Fish Diseases/prevention & control
  • Fish Diseases/virology
  • Gene Expression Regulation, Viral/drug effects
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Zebrafish/virology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Untranslated Regions/genetics
  • Blotting, Western
  • Disease Models, Animal
  • Gene Amplification/drug effects
(all 40)
PubMed
21857967 Full text @ PLoS One
Abstract
Screening and evaluating anti- hepatitis C virus (HCV) drugs in vivo is difficult worldwide, mainly because of the lack of suitable small animal models. We investigate whether zebrafish could be a model organism for HCV replication. To achieve NS5B-dependent replication an HCV sub-replicon was designed and created with two vectors, one with HCV ns5b and fluorescent rfp genes, and the other containing HCV's 52UTR, core, 32UTR and fluorescent gfp genes. The vectors containing sub-replicons were co-injected into zebrafish zygotes. The sub-replicon amplified in liver showing a significant expression of HCV core RNA and protein. The sub-replicon amplification caused no abnormality in development and growth of zebrafish larvae, but induced gene expression change similar to that in human hepatocytes. As the amplified core fluorescence in live zebrafish was detectable microscopically, it rendered us an advantage to select those with replicating sub-replicon for drug experiments. Ribavirin and oxymatrine, two known anti-HCV drugs, inhibited sub-replicon amplification in this model showing reduced levels of HCV core RNA and protein. Technically, this method had a good reproducibility and is easy to operate. Thus, zebrafish might be a model organism to host HCV, and this zebrafish/HCV (sub-replicon) system could be an animal model for anti-HCV drug screening and evaluation.
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Citation
Ding, C.B., Zhang, J.P., Zhao, Y., Peng, Z.G., Song, D.Q., and Jiang, J.D. (2011) Zebrafish as a potential model organism for drug test against hepatitis C virus. PLoS One. 6(8):e22921.