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

Animals
Untranslated Regions/genetics
Larva/genetics
Larva/metabolism
Larva/virology
Humans
Disease Models, Animal
Hepatocytes/drug effects
Hepatocytes/metabolism
Hepatocytes/virology
Drug Evaluation, Preclinical/methods*
Alkaloids/pharmacology
Hepacivirus/drug effects*
Hepacivirus/genetics
Hepacivirus/metabolism
Gene Amplification/drug effects
Ribavirin/pharmacology
Microscopy, Fluorescence
Hepatitis C/genetics
Hepatitis C/metabolism
Hepatitis C/prevention & control
Gene Expression Regulation, Viral/drug effects
Viral Nonstructural Proteins/genetics
Viral Nonstructural Proteins/metabolism
In Situ Hybridization
Genetic Vectors/administration & dosage
Genetic Vectors/genetics
Microinjections
Reverse Transcriptase Polymerase Chain Reaction
Green Fluorescent Proteins/genetics
Green Fluorescent Proteins/metabolism
Fish Diseases/prevention & control
Fish Diseases/virology
Replicon/genetics
Quinolizines/pharmacology
Blotting, Western
Antiviral Agents/pharmacology*
Zebrafish/genetics
Zebrafish/metabolism
Zebrafish/virology*

(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.

Genes / Markers

Figures