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. 2022 Dec 1;13:1034968. doi: 10.3389/fimmu.2022.1034968

Table 1.

Animal models for HBV researches.

Animal species Hepadna-virus Naturally Susceptible Experimental infection mode Advantages and disadvantages
Mouse (45) HBV No HBV transgenic
mouse model
The HBV transgenic mouse model can be widely used for several preclinical HBV antiviral evaluations in vivo. However, HBV transgenic mice revealed innate immune tolerance to HBV, while no covalently closed circular cccDNA was detected.
Humanized Chimera Mouse The best model for studying HBV persistence is the humanized xenograft model, albeit it is limited by a high degree of immune-deficiency.
Chimpanzee ( 46) HBV Yes Can be directly infected It can accurately simulate the pathogenesis and disease progression caused by human HBV. However, the availability constraints, high associated costs, and considerable ethical concerns have limited their use as experimental models.
Capuchin monkey ( 34) HBV Yes Can be directly infected Capuchin monkeys are highly endangered, have limited availability, are of xenogeneic origin, and have poorly characterized immune systems.
Rhesus macaques ( 44) HBV No Exogenous expression of human NTCP on the surface of hepatocytes It is the only available, non-endangered HBV NHP model. However, it is not susceptible to HBV infection, which has a low level of replication.
Tupaia ( 44) HBV Yes Can be directly infected It is very sensitive to HBV, but has the genetic heterogeneity of outbred species, the overall virus titer in vivo is low, and the research tools and materials for this species are scarce.
Woolly monkey ( 43) WMHBV Yes Can be directly infected The species is highly endangered and impossible to study.
Woodchuck ( 40) WHBV Yes Can be directly infected It has long been applied as a model to explore the biology and pathogenesis of hepatophilic DNA viruses as well as to evaluate antiviral drugs. However, the viral sequence homology between WHBV and HBV is limited, and the reagents used to characterize the immune system of marmots are insufficient.
Duck ( 41) DHBV Yes Can be directly infected DHBV can effectively replicate after infection, and infected cells can release infectious virus particles. However, the viral sequence homology between DHBV and HBV is limited, and ducks are distant from humans.