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

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 desig...

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Main Authors: Cun-Bao Ding, Jing-Pu Zhang, Ye Zhao, Zong-Gen Peng, Dan-Qing Song, Jian-Dong Jiang
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0022921&type=printable
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author Cun-Bao Ding
Jing-Pu Zhang
Ye Zhao
Zong-Gen Peng
Dan-Qing Song
Jian-Dong Jiang
author_facet Cun-Bao Ding
Jing-Pu Zhang
Ye Zhao
Zong-Gen Peng
Dan-Qing Song
Jian-Dong Jiang
author_sort Cun-Bao Ding
collection DOAJ
description 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 5'UTR, core, 3'UTR 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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spelling doaj-art-0524b8c467e8486c9d4eeff3fd43d1c92025-08-20T02:13:15ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0168e2292110.1371/journal.pone.0022921Zebrafish as a potential model organism for drug test against hepatitis C virus.Cun-Bao DingJing-Pu ZhangYe ZhaoZong-Gen PengDan-Qing SongJian-Dong JiangScreening 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 5'UTR, core, 3'UTR 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0022921&type=printable
spellingShingle Cun-Bao Ding
Jing-Pu Zhang
Ye Zhao
Zong-Gen Peng
Dan-Qing Song
Jian-Dong Jiang
Zebrafish as a potential model organism for drug test against hepatitis C virus.
PLoS ONE
title Zebrafish as a potential model organism for drug test against hepatitis C virus.
title_full Zebrafish as a potential model organism for drug test against hepatitis C virus.
title_fullStr Zebrafish as a potential model organism for drug test against hepatitis C virus.
title_full_unstemmed Zebrafish as a potential model organism for drug test against hepatitis C virus.
title_short Zebrafish as a potential model organism for drug test against hepatitis C virus.
title_sort zebrafish as a potential model organism for drug test against hepatitis c virus
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0022921&type=printable
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