One of the most well validated uses of humanized liver models is the ability to infect them with hepatotropic viruses and parasites. In this experimented, we wished to observe the effects of entecavir (ETV) dosing on virial titer in hepatitis B (HBV) infected animals. Experimentally, the mid-repopulated (~50%) FRG® KO mice were inoculated initially with HBV infected patient serum, and again to boost infection, and allowed to reach a stable level of infection at a point of 25 days post-infection. Experimentally, we note that high viral titer (10^9) HBV serum establishes stable infection much more rapidly than a titer of 10^8. Infection was monitored in blood by measuring HBV DNA with qPCR.
At 25 days post inoculation, ETV was administered orally in two groups at 0.02 mpk and 0.05 mpk for two weeks and viral titer levels were measured as previously described. As expected, post administration viral titer levels of the 0.05 mpk group lagged slightly in viral recovery and by two weeks after the final ETV dosing, viral titer has recovered by 10-fold. Towards the end of the study, the animals were sacrificed to confirm the disappearance of cccDNA.
Serial liver sectioning on the 90th day post infection demonstrate the expected human specific staining pattern of FAH (A), HBcAg (B), and HBSAg (C) conjugated respectively with HRP, HRP, and AP.