Original Article
Copyright ©2010 Baishideng. All rights reserved.
World J Gastroenterol. Apr 28, 2010; 16(16): 1979-1985
Published online Apr 28, 2010. doi: 10.3748/wjg.v16.i16.1979
Application of hepatitis B virus replication mouse model
Zhan Gao, Feng-Jun Liu, Li Liu, Tao-You Zhou, Jun Lei, Lu Xu, Cong Liu, Jie Dai, En-Qiang Chen, Hong Tang
Zhan Gao, Feng-Jun Liu, Li Liu, Tao-You Zhou, Jun Lei, Lu Xu, Cong Liu, Jie Dai, En-Qiang Chen, Hong Tang, Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China; Division of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041, Sichuan Province, China
Feng-Jun Liu, Department of Infection, the Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
Author contributions: Tang H designed the research and provided fundamental support; Gao Z, Liu FJ, Liu L, Liu C, Lei J, Xu L, Zhou TY and Dai J performed the research; Gao Z and Chen EQ analyzed data; Gao Z and Chen EQ wrote the paper.
Supported by The National Basic Research Program of China, No. 2007CB512902 and No. 2006CB504302; and Key Technologies Research of Sichuan Province, No. 2008SZ0039
Correspondence to: Hong Tang, Professor, Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China. htang6198@hotmail.com
Telephone: +86-28-85422647 Fax: +86-28-85423052
Received: January 7, 2010
Revised: February 7, 2010
Accepted: February 14, 2010
Published online: April 28, 2010
Abstract

AIM: To evaluate the value of the hepatitis B virus (HBV) replication mouse model with regard to several aspects of the study of HBV biology.

METHODS: To evaluate the HBV replication mouse model in detecting the efficacy of anti-HBV agents, the interferon inducer polyinosinic-polytidylin acid (polyIC) and nucleotide analogues adefovir and entecavir were administered to mice injected with wild type pHBV4.1, and the inhibiting effect of these agents on HBV DNA replication was evaluated. To identify the model’s value in a replication ability study of HBV drug-resistant mutants and a HBx-minus mutant, telbivudine resistance mutants (rtM204I, ayw subtype), adefovir resistance mutants (rtA181V + rtN236T, ayw subtype) and HBx-minus mutants were injected respectively, and their corresponding HBV DNA replication intermediates in mouse liver were assessed.

RESULTS: Compared with the wild type HBV replication mouse model without antiviral agent treatment, the HBV DNA replication intermediates of the polyIC-treated group were decreased 1-fold; while in the entecavir- and adefovir-treated groups, the levels of HBV DNA replication intermediates were inhibited 13.6-fold and 1.4-fold, respectively. For the mouse models injected with telbivudine resistance mutant, adefovir resistance mutant and HBx-minus mutant, HBV DNA replication intermediates could still be detected, but the levels of HBV DNA replication intermediates of these mutants decreased 4.5-fold, 5.6-fold and 2.9-fold respectively, compared with the mouse model with wild type HBV plasmid.

CONCLUSION: The HBV replication mouse model we established was a useful and convenient tool to detect the efficacy of antiviral agents and to study the replication ability of HBV mutants in vivo.

Keywords: Hepatitis B virus; Antiviral agents; Drug resistance; Mutants; Mouse model