单位：[1]Experimental Medicine Center,Tongji Hospital of Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China.华中科技大学同济医学院附属同济医院科研平台[2]Department of Infectious Diseases, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.华中科技大学同济医学院附属协和医院[3]Department of Infectious Disease, Anhui Provincial Hospital, Anhui Medical University, Hefei, China.[4]Institute of Virology, University Hospital of Essen, University Duisburg-Essen, Essen, Germany.
Background: Hydrodynamic injection (HI) of hepatitis B virus (HBV) mouse model is an useful tool for HBV related research in vivo. However, only 40% of C57/BL6 mice injected with 10 mu g HBV genome contained plasmid (pAAV-HBV1.2), serum HBsAg more than 6 months and none of the BALB/c mice injected with 10 mu g pAAV-HBV1.2 plasmid DNA, serum HBsAg positive more than 4 weeks in the previous study. Methods: In this study, C57/ BL6 and BALB/c mice were hydrodynamic injected with different doses of pAAV-HBV1.2 plasmid DNA. HBV related serum markers were detected by ELISA. ALT levels in the serum were measured using full automated biochemistry analyzer. HBcAg positive cells in the liver were detected by immunohistochemical staining. The mRNA levels of IRF3, ISGs including ISG15, OAS, PKR and immune factors including IFN gamma, TNF alpha, TGF beta, IL-6, IL-10, PDL1 in liver of the mice were quantified by qRT-PCR. Results: The results showed that the mice injected with 100 mu g high-concentration or 1 mu g low-concentration of pAAVHBV1.2 plasmid DNA did not excert dominant influence on HBV persistence. In contrast, injection of 5 mu g intermediatedose of pAAV-HBV1.2 plasmid DNA led to significant prolonged HBsAg expression and HBV persistence in both C57/BL6 (80% of the mice with HBsAg positive more than 6 months) and BALB/c (60% of the mice with HBsAg positive more than 3 months) mice. IFN. was significant up-regulated in liver of the mice injected with 1 mu g or 100 mu g pAAV-HBV1.2 plasmid DNA. TNFa was up-regulated significantly in liver of the mice injected with 100 mu g pAAV-HBV1.2 plasmid DNA. Moreover, PDL1 was significant up-regulated in liver of the mice injected with 5 mu g pAAV-HBV1.2 plasmid DNA. Conclusion: In this paper we demonstrated that, in the HBV HI mouse model, the concentration of injected pAAV-HBV1.2 plasmid DNA contributes to the diverse kinetics of HBsAg and HBeAg in the serum as well as HBcAg expression level in the liver, which then determined the HBV persisternce, while the antiviral factors IFN gamma, TNF alpha as well as immune negative regulatory factor PDL1 play important roles on HBV persistence.
基金：
National Science and Technology Major Project for Infectious Diseases of China [2012ZX10004503]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81201289]; International Science & Technology Cooperation Program of China [2011DFA31030]; Deutsche ForschungsgemeinschaftGerman Research Foundation (DFG) [DFG Transregio TRR60]
第一作者单位：[1]Experimental Medicine Center,Tongji Hospital of Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China.[3]Department of Infectious Disease, Anhui Provincial Hospital, Anhui Medical University, Hefei, China.
通讯作者：
推荐引用方式(GB/T 7714)：
li lei,li sheng,zhou yun,et al.The dose of HBV genome contained plasmid has a great impact on HBV persistence in hydrodynamic injection mouse model[J].VIROLOGY JOURNAL.2017,14:doi:10.1186/s12985-017-0874-6.
APA：
li,lei,li,sheng,zhou,yun,yang,lu,zhou,di...&song,jingjiao.(2017).The dose of HBV genome contained plasmid has a great impact on HBV persistence in hydrodynamic injection mouse model.VIROLOGY JOURNAL,14,
MLA：
li,lei,et al."The dose of HBV genome contained plasmid has a great impact on HBV persistence in hydrodynamic injection mouse model".VIROLOGY JOURNAL 14.(2017)
