General Information

Development

The rAAV-HBV model is a model of mice infected with whole genomic DNA of HBV carried by recombinant adeno-associated virus (rAAV) vectors. It was constructed as follows:

Using the hepatophilic type 8 rAAV as a vector, a DNA fragment of about 1.3 times the length of the HBV genome was injected intravenously, which could carry out HBV replication in the liver of mice and produce HBV virus particles.

After rAAV-HBV injection, mouse serum HBsAg, HBeAg and HBV DNA as well as liver group HBcAg were stably expressed for more than 8 months, and its expression level increased with the increase of recombinant viral injection dose; the high dose of the injection could cause more than 40% of the hepatocytes infected, and the copy number of HBV DNA in the serum could reach more than 106 IU/mL. The phenotype of rAAV-HBV infection varied among mouse strains, with higher HBV viral titers in C57BL/6 mice than in BALB/c mice. Male mice are usually infected with higher HBV viral titers than female mice. Intact, infectious viral particles are produced in this mouse, and the level of HBV replication is comparable to that of a chronic hepatitis B patient. In addition to high titers of HBV DNA, high levels of HBsAg and HBeAg are detected in the peripheral blood.

Phenotype

1. Detection of serum HBV index and liver tissue ICH in AAV-HBV type D mice

Fig 1. Serum HBV index and liver tissue IHC detection (HBcAg and HBsAg) of AAV-HBV-type D mice.

2. Detection of serum HBsAg levels in AAV-HBV (genotype D) mice (B6) with different inoculations

Fig2. Detection of serum HBsAg levels in AAV-HBV (genotype D) mice (B6) with different inoculations

3. Serum HBV indexes of AAV-HBV (genotype D) mice (B6) with different inoculations

Fig 3. serum HBV index levels in AAV-HBV mice with different inoculations

4. AAV-HBV (type C) mice serum HBV indexes

Fig 4. HBV DNA, HBeAg and HBsAg levels in serum of mice with AAV-HBV type C (5E10)

5. AAV-HBV (type B) mice serum HBV indexes

Fig 5. HBV DNA, HBeAg and HBsAg levels in serum of mice with AAV-HBV type B.

6. Serum HBV markers in B6-hPD-1 mice infected with AAV-HBV

Fig 6. Serum HBV DNA, HBeAg, and HBsAg levels in hPD-1 mice infected with AAV-HBV type D. The various indicators of HBV remain at a high level for a long time, up to 26 weeks.

AAV-HBV mice applications

1. Study on Anti-HBV Drugs in AAV-HBV Mice

Fig 7. Anti-HBV activity of propofol tenofovir (TAF).

AAV-HBV Mice Applications

1. the model can be used to study HBV, therapeutic drugs and vaccines and further downstream in chronic hepatitis and fibrosis (combined with chemical induction).

2. it provides an excellent model for studying viral and host factors affecting HBV replication, pathogenetic genes and physiological processes.