Application of hepatitis B virus replication mouse model.
OBJECTIVE
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.


CONCLUSIONS
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.
Gao
Zhan
Z
Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China.
Liu
Feng-Jun
FJ
Liu
Li
L
Zhou
Tao-You
TY
Lei
Jun
J
Xu
Lu
L
Liu
Cong
C
Dai
Jie
J
Chen
En-Qiang
EQ
Tang
Hong
H
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D004195:Disease Models, Animal; D024882:Drug Resistance, Viral; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006509:Hepatitis B / Q000821:virology*; D006515:Hepatitis B virus / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000473:pathology / Q000821:virology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D009705:Nucleosides / Q000494:pharmacology; D011744:Pyrimidinones / Q000494:pharmacology; D000077712:Telbivudine; D013936:Thymidine / Q000031:analogs & derivatives; D014779:Virus Replication
D000998:Antiviral Agents; D009705:Nucleosides; D011744:Pyrimidinones; D000077712:Telbivudine; D013936:Thymidine