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[Comparison of HBV persistent infection mice models by different serotypes of AAVs carrying HBV genomes]
Abstract:
In recent years, Hepatitis B virus (HBV) persistent infection mouse model with recombinant adeno-associated virus 8 carrying 1.3 copies of HBV genome (rAAV8-1.3HBV) is concerned. We studied and compared the efficacy among HBV persistent infection mice models by other serotypes except AAV8. First, we prepared and purified five viruses: rAAV1-1.3HBV, rAAV2-1.3HBV, rAAV5-1.3HBV, rAAV8-1.3HBV and rAAV9-1.3HBV. Then we injected each virus into 3 C57BL/6J mice with the dose of lx 1011 vg (Viral genome, vg) per mouse. We detected HBsAg and HBeAg in sera by enzyme-linked immunosorbent assay (ELISA) at different time points post injection. We killed mice 8 weeks post injection and took blood and livers for assay. We detected copies of HBV DNA by real-time quantitative PCR in sera and livers. Meantime, we detected HBcAg in the livers of mice by immunohistochemistry and further performed pathology analysis of these livers. The five groups of mice, HBeAg and HBsAg expression sustained 8 weeks in serological detection and HBV DNA was both detected in sera and livers at the time of 8 weeks post injection. HBeAg, HBsAg, HBV DNA copies expression levels in descending order were AAV8>AAV9>AAV1>AAV5>AAV2. HBcAg expression was detected in livers as well. Varied degrees of liver damage were shown in five groups of mice. This study provides more alternative AAV vector species to establish a persistent infection with hepatitis B model.
Insights
This study compared adeno-associated virus (AAV) serotypes for creating Hepatitis B virus (HBV) infection models. AAV8 and AAV9 demonstrated the highest efficacy in establishing persistent HBV infection in mice.
Area of Science:
- Virology
- Immunology
- Genetics
Background:
- Persistent Hepatitis B virus (HBV) infection mouse models are crucial for research.
- Recombinant adeno-associated virus serotype 8 (rAAV8) carrying the HBV genome is a common tool.
- Alternative AAV serotypes for model development require investigation.
Purpose of the Study:
- To compare the efficacy of different AAV serotypes in establishing a persistent HBV infection mouse model.
- To evaluate HBV markers and liver pathology across various AAV serotypes.
Main Methods:
- Prepared and purified five AAV serotypes (AAV1, AAV2, AAV5, AAV8, AAV9) carrying 1.3 copies of the HBV genome.
- Injected each virus into C57BL/6J mice and monitored HBsAg and HBeAg via ELISA.
- Assessed HBV DNA, HBcAg expression, and liver pathology 8 weeks post-injection.
Main Results:
- All tested AAV serotypes established persistent HBV infection, with sustained HBsAg and HBeAg expression for 8 weeks.
- HBV DNA was detected in sera and livers across all groups.
- Efficacy in terms of HBeAg, HBsAg, and HBV DNA levels followed the order: AAV8 > AAV9 > AAV1 > AAV5 > AAV2.
- HBcAg expression was observed in livers, and varying degrees of liver damage were noted.
Conclusions:
- Multiple AAV serotypes can be used to establish persistent HBV infection mouse models.
- AAV8 and AAV9 are the most effective serotypes for this purpose.
- This research expands the options for creating HBV infection models for scientific study.
