AAV-HBV Transfection Mouse Model Efficient for Animal Experiments and HBV-Related Studies

Despite the availability of effective vaccination, hepatitis B virus (HBV) infection continues to be a major challenge worldwide. The exceptionally limited host spectrum of HBV has limited the research progress. Therefore, the development of HBV mouse models can be used for the study of infection, immune responses, pathogenesis and antiviral therapies. Among them, the use of adeno-associated virus (AAV) vector carrying 1.3 times the full-length genome of HBV to prepare a mouse animal model of HBV persistent infection by tail vein injection is simple to prepare, with high success rate, homogeneous and stable, and wide applicability, which can be effectively used in HBV-related studies.

AAV-HBV Transfection Mouse Model

Adeno-associated viral (AAV) vector-mediated transfection mouse model is based on viral transduction by intravenous injection hepatotropic viral vectors containing 1.2- to 1.3-fold HBV genomes. In this model, HBV genome is inserted to the genome of viral vectors, which initiates HBV replication and secretion of infectious HBV virions. This vector model expresses HBV replication intermediates. AAV belongs to the family Parvoviridae, which is characterized by site-specific integration, natural deficiency, and low immunogenicity. AAV has a variety of serotypes, each of which has organ specificity, making it an ideal gene-targeting vector. Studies have shown that the liver transduction efficiency of AAV8 is stronger than that of AAV1, AA5, and AA6 serotypes, indicating that AAV8 is highly hepatotropic. This feature is favorable for the application of AAV8 in HBV-related studies.

Advantages of AAV as HBV Carrier

High security

Compared with Ad-HBV, AAV-HBV vectors have minimal AAV genomes with only the essential AAV inverted terminal repeat sequence that is responsible for viral packaging and does not encode any AAV viral proteins. Thus, this vector has a clean background and does not induce an obvious non-HBV immune response, making it a more suitable tool to establish persistent HBV infection.

Long-term transduction

The AAV-HBV mouse model allows more efficient and homogeneous HBV transduction with ~60% of hepatocytes expressing HBcAg 12 weeks after injection. Serum HBsAg in AAV-HBV mice remains at relative high levels even in 3 or 4 months. Therefore, the AAV-HBV mouse model is preferred to evaluate therapeutic vaccines for chronic infection and the antiviral effects of TLR agonists like the TLR9 ligand CpG.

Organ specificity

The coat proteins of different serotypes of AAV recognize different receptors on the cell surface, thus the efficiency of infiltration into different tissue cells varies greatly and exhibits certain organ-targeting specificity. Among them, AAV8 is the strongest hepatophilic type among the currently applied AAV vectors and is often used in liver-related studies.

Creative Biogene offers HBV genome AAV particles based on AAV vectors that can be applied directly, easily and efficiently to develop mouse models of HBV infection. Our products, which include the following, can help researchers save time and cost in generating and validating constructs of recombinant AAV-HBV vectors so that scientists can spend more effort on solving major problems.

Product Name	Description
HBV-D/ayw AAV (Serotype 8)	The most widely distributed, can produce HBV DNA, HBeAg, HBsAg, suitable for cellular experiments and animal experiments.
HBV-C/adr AAV (Serotype 8)	Strong pathogenicity, can produce HBV DNA, HBeAg, HBsAg, suitable for cellular experiments and animal experiments.
HBV-C/RD AAV (Serotype 8)	This replication-deficient AAV-HBV virus carries a mutated reverse transcriptase active site in the polymerase region, and pgRNA has lost its ability to reverse transcribe into DNA. It can produce HBeAg, HBsAg, and is suitable for HBV curative drug development.
HBV-B/adw AAV (Serotype 8)	Weaker pathogenicity than type C, can produce HBV DNA, HBeAg, HBsAg, suitable for cellular and animal experiments.

Applications of the Viral Vector-Mediated Transfection Mouse Model

AAV-HBV transfection mouse models can establish persistent HBV replication for more than 3 months or even more than 1 year and is widely used in HBV drug studies. Prof. Xiaobing Wu's group developed a persistent HBV replication mouse model by transduction of recombinant AAV8 (rAAV8)-HBV 1.3 into C57BL/6 mice. This model is also used to evaluate antiviral effects of NAs such as entecavir and lamivudine.

Moreover, two studies reported fibrosis in HBV mice transfected with AAV8-HBV1.2, which is one of the few replicative models that can be used to study the mechanism of liver fibrosis in the course of chronic hepatitis B.

Fig. 1 Schematic illustration of the AAV vector used to transfer the HBV genome and in vitro determination of the replication ability of the construct. (Ye, et al., 2015)

References:

Du, Y.; et al. In Vivo Mouse Models for Hepatitis B Virus Infection and Their Application. Front Immunol. 2021 Oct 29; 12:766534.
Dong, X. Y.; et al. Establishment of Hepatitis B Virus Chronic Infection Mouse Model by In Vivo Transduction with a Recombinant Adeno-Associated Virus 8 Carrying 1.3 Copies of HBV Genome. Chin J Virol. 2010, 26:425–31.
Wang, G. J.; et al. Anti-HBV Effect of Nucleotide Analogues on Mouse Model of Chronic HBV Infection Mediated by Recombinant Adeno-Associated Virus 8. Chin J Biotechnol. 2013, 29:95–106.
Kan, F.; et al. Proteomic and Transcriptomic Studies of HBV-Associated Liver Fibrosis of an AAV-HBV-Infected Mouse Model. BMC Genomics. 2017, 18:641.
Ye, L.; et al. Adeno-Associated Virus Vector Mediated Delivery of the HBV Genome Induces Chronic Hepatitis B Virus Infection and Liver Fibrosis in Mice. PloS One. 2015, 10: e130052.

* For research use only. Not intended for any clinical use.

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AAV-HBV Transfection Mouse Model Efficient for Animal Experiments and HBV-Related Studies