Establishment Of A Mouse Model Stably Replicating HBV By RAAV-HBV

Hepatitis B virus(HBV)infection is one of the most serious global viral diseases.Especially in China,the patients with chronic hepatitis B.account for one-third of the total patients in the world,but effective drug treatment is lacking in this disease.At present,the available drugs have obvious side effects and drug resistance.Lacking of appropriate animal models has contributed to an important reason for the slow rate of development of anti-hepatitis B drugs,especially the lack of the chronic hepatitis B infection mice models.This study attempted to establish an HBV mouse model suitable for drug screening by employing the latest rAAV-HBV recombinant virus.We injected the recombinant virus rAAV-HBV into C57BL/6 mice via the tail vein.After stable replication of the HBV virus,we started gavage with entecavir(ETV)in the mice of dosing group and the drug concentration is 3.2 mg/kg ETV for a duration of 7 days.Subsequently,HBV replication was detected after 9 weeks.The results show that the expression of HBe Ag,HBs Ag,and HBV DNA were all negative in the control group;But the expression in the infected group were all positive,and continued to high levels until the experiment is completed;The expression of HBe Ag and HBs Ag in the drug-supplemented mice was all positive until the end of the experiment,and the expression level of HBV DNA decreased 100-fold after the drug was administered.This result indicates that the rAAV-HBV can be continuously replicated and expressed in the liver of mice,and shows a good drug response to the specific drug entecavir,which truly reflects the characteristics of the drug action,that is,exclusively inhibits viral reverse transcriptase and has no effect on other viral indicators.Therefore,the model construction was successful,which fully prepared for the follow-up drug screening in the laboratory.