Table 1:
Comparison of different animal model for HBV
| HBV life-cycle supported? | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| species | model | entry | replication | assembly/release | Immune status | throughput | costs | utility | caveats |
| mouse | 1.3x HBV transgenic | no | yes* | yes | immunocompetent but tolerized to HBV | high | low | immune-responses, some pathogenesis | not an authentic infection model |
| AAV-/AdV-HBV | no | yes* | yes | immunocompetent | high | low | immune responses, immunomodulators | not an authentic infection model | |
| hNTCP transgenic/knock-in | yes | no | no | immunocompetent | high | low | entry inhibitors? | only entry | |
| human liver chimeric | yes | yes** | yes | immunodeficient | medium | medium | testing of DAAs and some HTAs | immunodeficient | |
| dually engrafted human liver/immune system mice | yes | yes** | yes | immunocompetent | medium | medium | immune-responses, some pathogenesis, immunomodulators | heterogeneity, limited immune functionality | |
| Rhesus macaque |
AAV-hNTCP | yes | yes** | yes | immunocompetent | low | high | immune-responses | only low level, transient viremia |
| Tree shrews |
HBV | yes | yes** | yes | immunocompetent | low | medium | TBD | weak, short-lived viremia with limited viral replication |
| Woolly monkey |
WMHBV | yes | yes** | yes | immunocompetent | low | n/a | n/a | surrogate virus, endangered species, not accessible |
| Spider monkeys |
WMHBV | yes | yes** | yes | immunocompetent | low | n/a | n/a | surrogate virus, endangered species, not routinely available for research |
| Squirrel monkey |
HBV/WMHBV | yes | yes** | yes | immunocompetent | low | high | n/a | surrogate virus, only low level, transient WMHBV viremia, limited availability of tools |
| woodchuck | WHBV | yes | yes** | yes | immunocompetent | low | high | vaccine development, assessing immunologic aspects of the disease, and evaluating antiviral therapies | surrogate virus, difficult to access, limited availability of tools |
| ducks | DHBV | yes | yes** | yes | immunocompetent | high | high | vaccine development, assessing immunologic aspects of the disease, and evaluating antiviral therapies | surrogate virus, limited availability of tools |
*
does not occur exactly as de novo HBV replication.
**
denotes clear evidence for cccDNA formation
AdV, adenovirus; AAV, adeno associated virus; cccDNA, covalently closed circular DNA; DAA, directly acting antiviral; DHBV, duck HBV; HBV, hepatitis B virus; HtA, host targeting antiviral; WMHBV, woolly monkey HBV; WHBV, woodchuck HBV