Chronic hepatitis B (CHB) is caused by hepatitis B virus (HBV) infection and related liver cirrhosis (L.C). Hepatocellular carcinoma (HCC) and liver failure are important medical and public health problems worldwide. The Hepatitis B virus is genus-specific and tissue-specific and can be excreted in various body fluids, such as blood, semen, vaginal secretions, saliva, breast milk, menstruation, tears, urine, and sweat. The establishment of suitable experimental animal models for hepatitis B virus (HBV) infection is of great significance for the screening of anti-hepatitis B drugs, exploring the mechanism of HBV infection, and finding effective prevention and treatment methods. At present, animal models of hepatitis B include the non-human primate HBV model, tree shrew HBV model, duck HBV model, dry otter HBV model, and mouse HBV model.
Contemporary developments in virology, molecular biology, immunology, and other related disciplines have greatly promoted the study of animal models of HBV infection. Ace Therapeutics can provide customization services for hepatitis B virus models. Currently, a variety of custom hepatitis B virus models are available, including hepatitis B models for groundhogs, tree shrews, ducks, woodchucks, and mice. These models can be used to study HBV replication at the molecular level, to evaluate antiviral drugs at the preclinical level, to study drug efficacy, pharmacokinetics, and toxicology, and to evaluate the efficacy of immunotherapy.
[Modelling mechanism] Hepatitis B virus (HBV) is mainly transmitted through blood and blood products using HBV patient's serum or HBV DNA, which is injected into animals by intravenous injection or hydrodynamic high-pressure injection.
[Modeling method] 0.5ml of serum from hepatitis B patients positive for both hepatitis B virus surface antigen (HBsAg) and hepatitis B virus e antigen (HBeAg) were inoculated into tree shrews via the femoral vein.
[Model characteristics] After HBV infection, HBsAg, anti-HBs, or HBV DNA could be detected in blood; HBsAg and/or HBcAg could be detected by immunohistochemistry of liver tissues; serum ALT was elevated; HBV DNA in integrated form could be detected in liver tissues by Southern blotting. The tree shrew model is low cost, convenient for experimental operation, and not subject to tree shrew model is low cost, easy to operate, and not subject to strict animal ethical restrictions.
[Model evaluation and application] Newborn tree shrews are inoculated with human HBV, and the virus can exist and replicate stably in the animal for a long time. The tree shrew is expected to be a reliable animal model for human HBV.
[Modeling method] The duck hepatitis B virus (DHBV) was injected into ducks by intravenous, intramuscular, intraperitoneal, intrahepatic, and intravenous injections of duck embryos.
[Model characteristics] The infection rate of 1-day-old ducks can be close to 100% after DHBV inoculation, the viremia can be maintained for a long time, and DHBV DNA can be detected in the liver. 5 days old after inoculation, DHBV DNA and endogenous DNA polymerase activity decreased, and 14 days old after inoculation, no viremia was produced. After infection with the virus, the body can simultaneously develop the corresponding virus-specific humoral and cellular immune responses, producing duck DHBsA9. and can be maintained for 22 weeks.
[Model evaluation and application] The duck model DHBV infection rate is high, easy to feed, and is a good model for assessing the efficacy of preclinical antiviral drug therapy. However, DHBV is an avian hemophilic virus that is structurally different from human HBV, and ducks are evolutionarily different from humans, so it does not reproduce the human HBV infection process well.
[Modeling method] Woodchuck hepatitis virus (WHV) is another hemophilic DNA virus found after human HBV. Chronic infection with WHV in otters can gradually develop into severe hepatitis and liver cancer, which is very similar to the development process of HBV infection in humans. A model of hepatitis in otters can be obtained by inoculating young otters with WHV.
[Model characteristics] After infection with WHV, WHsAg antigenemia occurs, and characteristic WHV surface and core particles are visible under electron microscopy.
[Model evaluation and application] WHV infections in neonatal woodchucks are mostly chronic and can be used to study the chronicity mechanism of HBV, for the development of HBV vaccines and antiviral drugs, and for studies related to the life cycle, molecular mechanism, infection and cancer mechanism of HBV. However, the animal model of dry otter hepatitis virus cannot be directly infected with HBV, and there are still some differences between WHV and HBV, which cannot fully simulate the pathological process of HBV.
[Modeling method] HBV plasmid DNA was injected into the tail vein of mice by high-pressure hydrodynamic method, and HBV DNA could be detected in the serum after injection.
[Model characteristics] After HBV infection, the viral titer is high, HbsAg can be maintained in vivo for more than 6 months, and HBV replication transcription intermediates can be continuously detected in vivo for up to 1 year.
[Model evaluation and application] The hydrodynamic method transfected mouse model can be used to study HBV life history and chronic infection mechanism, and can specifically localize mutant HBV-DNA to study the mechanism of single or multiple genes in the process of HBV infection; meanwhile, because it is immunocompetent mice, it can be used to study the mechanism of immune effect caused by the virus.
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