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Conditional Inducible Triple-Transgenic Mouse Model for Rapid Real-Time Detection of HCV NS3/4A Protease Activity

Hepatitis C virus (HCV) frequently establishes persistent infections that can develop into severe liver disease. The HCV NS3/4A serine protease is not only essential for viral replication but also cleaves multiple cellular targets that block downstream interferon activation. Therefore, NS3/4A is an... Full description

Journal Title: PLoS One Mar 2016, Vol.11(3), p.e0150894
Main Author: Yao, Min
Other Authors: Lu, Xin , Lei, Yingfeng , Yang, Jing , Zhao, Haiwei , Qiao, Qinghua , Han, Peijun , Xu, Zhikai , Yin, Wen
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 19326203 ; DOI: 10.1371/journal.pone.0150894
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title: Conditional Inducible Triple-Transgenic Mouse Model for Rapid Real-Time Detection of HCV NS3/4A Protease Activity
format: Article
creator:
  • Yao, Min
  • Lu, Xin
  • Lei, Yingfeng
  • Yang, Jing
  • Zhao, Haiwei
  • Qiao, Qinghua
  • Han, Peijun
  • Xu, Zhikai
  • Yin, Wen
subjects:
  • Muridae
  • Gaussia
  • Infections
  • Hepatitis C Virus
  • Liver
  • Hepatitis
  • Mice
  • Hepatitis C
  • Doxycycline
  • Proteinase Inhibitors
  • Viruses
  • Genomes
  • Oral Administration
  • Liver Diseases
  • Monitoring
  • Drug Development
  • Transgenic Mice
  • Interferon
  • Rodents
  • Protease Inhibitors
ispartof: PLoS One, Mar 2016, Vol.11(3), p.e0150894
description: Hepatitis C virus (HCV) frequently establishes persistent infections that can develop into severe liver disease. The HCV NS3/4A serine protease is not only essential for viral replication but also cleaves multiple cellular targets that block downstream interferon activation. Therefore, NS3/4A is an ideal target for the development of anti-HCV drugs and inhibitors. In the current study, we generated a novel NS3/4A/Lap/LC-1 triple-transgenic mouse model that can be used to evaluate and screen NS3/4A protease inhibitors. The NS3/4A protease could be conditionally inducibly expressed in the livers of the triple-transgenic mice using a dual Tet-On and Cre/loxP system. In this system, doxycycline (Dox) induction resulted in the secretion of Gaussia luciferase (Gluc) into the blood, and this secretion was dependent on NS3/4A protease-mediated cleavage at the 4B5A junction. Accordingly, NS3/4A protease activity could be quickly assessed in real time simply by monitoring Gluc activity in plasma....
language: eng
source:
identifier: E-ISSN: 19326203 ; DOI: 10.1371/journal.pone.0150894
fulltext: fulltext_linktorsrc
issn:
  • 19326203
  • 1932-6203
url: Link


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titleConditional Inducible Triple-Transgenic Mouse Model for Rapid Real-Time Detection of HCV NS3/4A Protease Activity
creatorYao, Min ; Lu, Xin ; Lei, Yingfeng ; Yang, Jing ; Zhao, Haiwei ; Qiao, Qinghua ; Han, Peijun ; Xu, Zhikai ; Yin, Wen
ispartofPLoS One, Mar 2016, Vol.11(3), p.e0150894
identifierE-ISSN: 19326203 ; DOI: 10.1371/journal.pone.0150894
subjectMuridae ; Gaussia ; Infections ; Hepatitis C Virus ; Liver ; Hepatitis ; Mice ; Hepatitis C ; Doxycycline ; Proteinase Inhibitors ; Viruses ; Genomes ; Oral Administration ; Liver Diseases ; Monitoring ; Drug Development ; Transgenic Mice ; Interferon ; Rodents ; Protease Inhibitors
descriptionHepatitis C virus (HCV) frequently establishes persistent infections that can develop into severe liver disease. The HCV NS3/4A serine protease is not only essential for viral replication but also cleaves multiple cellular targets that block downstream interferon activation. Therefore, NS3/4A is an ideal target for the development of anti-HCV drugs and inhibitors. In the current study, we generated a novel NS3/4A/Lap/LC-1 triple-transgenic mouse model that can be used to evaluate and screen NS3/4A protease inhibitors. The NS3/4A protease could be conditionally inducibly expressed in the livers of the triple-transgenic mice using a dual Tet-On and Cre/loxP system. In this system, doxycycline (Dox) induction resulted in the secretion of Gaussia luciferase (Gluc) into the blood, and this secretion was dependent on NS3/4A protease-mediated cleavage at the 4B5A junction. Accordingly, NS3/4A protease activity could be quickly assessed in real time simply by monitoring Gluc activity in plasma....
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titleConditional Inducible Triple-Transgenic Mouse Model for Rapid Real-Time Detection of HCV NS3/4A Protease Activity
descriptionHepatitis C virus (HCV) frequently establishes persistent infections that can develop into severe liver disease. The HCV NS3/4A serine protease is not only essential for viral replication but also cleaves multiple cellular targets that block downstream interferon activation. Therefore, NS3/4A is an ideal target for the development of anti-HCV drugs and inhibitors. In the current study, we generated a novel NS3/4A/Lap/LC-1 triple-transgenic mouse model that can be used to evaluate and screen NS3/4A protease inhibitors. The NS3/4A protease could be conditionally inducibly expressed in the livers of the triple-transgenic mice using a dual Tet-On and Cre/loxP system. In this system, doxycycline (Dox) induction resulted in the secretion of Gaussia luciferase (Gluc) into the blood, and this secretion was dependent on NS3/4A protease-mediated cleavage at the 4B5A junction. Accordingly, NS3/4A protease activity could be quickly assessed in real time simply by monitoring Gluc activity in plasma....
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titleConditional Inducible Triple-Transgenic Mouse Model for Rapid Real-Time Detection of HCV NS3/4A Protease Activity
authorYao, Min ; Lu, Xin ; Lei, Yingfeng ; Yang, Jing ; Zhao, Haiwei ; Qiao, Qinghua ; Han, Peijun ; Xu, Zhikai ; Yin, Wen
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6Mice
7Hepatitis C
8Doxycycline
9Proteinase Inhibitors
10Viruses
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abstractHepatitis C virus (HCV) frequently establishes persistent infections that can develop into severe liver disease. The HCV NS3/4A serine protease is not only essential for viral replication but also cleaves multiple cellular targets that block downstream interferon activation. Therefore, NS3/4A is an ideal target for the development of anti-HCV drugs and inhibitors. In the current study, we generated a novel NS3/4A/Lap/LC-1 triple-transgenic mouse model that can be used to evaluate and screen NS3/4A protease inhibitors. The NS3/4A protease could be conditionally inducibly expressed in the livers of the triple-transgenic mice using a dual Tet-On and Cre/loxP system. In this system, doxycycline (Dox) induction resulted in the secretion of Gaussia luciferase (Gluc) into the blood, and this secretion was dependent on NS3/4A protease-mediated cleavage at the 4B5A junction. Accordingly, NS3/4A protease activity could be quickly assessed in real time simply by monitoring Gluc activity in plasma....
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