疾病动物模型,乙裂肝炎病毒动物模型 z-bio 2021-03-10 265

　　At present, the animal models of hepatitis B virus mainly include tree sh hepatitis B model, duck hepatitis B model, marmot hepatitis B model and mouse hepatitis B model.

　　[Modeling mechanism] Hepatitis B virus (HBV) is mainly transmitted through blood and blood products using HBV patient serum or HBV DNA, and injected into animals through intravenous high pressure injection or hydrodynamic high pressure injection.

　　[Modeling method]

　　Treeshrou: I inoculated 0.5 ml of hepatitis B patient serum from the femoral vein. These sera are positive for both hepatitis B virus surface antigen (HBsAg) and hepatitis B virus electronic antigen (HBeAg).

　　Duck: Duck hepatitis B virus (duck hepatitis B virus, DHBV) is injected into ducks by intravenous injection, intramuscular injection, intraperitoneal injection, intrahepatic injection and intravenous injection of duck embryo.

　　Marmot (Woodchuck): Marmot hepatitis virus (WHY) is another liver-directed DNA virus discovered after human HBV. Groundhogs infected with WHV for a long time can gradually develop severe hepatitis and liver cancer. This is very similar to the pathogenic process of human infection with HBV. You can obtain a woodchuck hepatitis model by inoculating young woodchucks with WHV. The mouse model of hydrodynamic transfection: The HBV plasmid DNA was injected into the tail vein of the mouse using the high-pressure hydrodynamic method, and the HBV DNA can be detected in the injected serum.

　　[Model Features]

　　tree shrew: After HBV infection, HBsAg, anti-HBs and HBV DNA are detected in the blood, and HBsAg and/or HBcAg are detected in the immunohistochemical examination of liver tissue. HBV DNA is integrated into liver tissue, ALT is elevated, and Southern blot can be detected. This kind of tree sh model is cheap, easy to operate, and is not strictly restricted by animal ethics.

　　Ducks: After inoculation with DHBV, the infection rate of 1-day-old ducks is close to 100%, viremia can be maintained for a long time, and DHBV DNA can also be detected in the liver. After 5 days of inoculation, the activities of DHBV DNA and endogenous DNA polymerase decreased, and no viremia was caused by 14 days of inoculation. After being infected with the virus, the human body has the corresponding virus-specific humoral and cell-mediated immune response at the same time, and may produce duck DHBsA9. And it can last for 22 weeks. Woodchuck: When infected with WHV, WHsAg antigenemia will occur, and the characteristic WHV surface and core particles can be seen through an electron microscope.

　　Hydrodynamic transfection mouse model: After HBV infection, the virus titer increases, HbsAg remains in the body for more than 6 months, and HBV replication transcription intermediates are continuously detected in the body for up to 1 year. .. [Model Evaluation and Application] 1996, Walter, etc. It is reported that during the newborn period, the tree sh has been vaccinated against human HBV. The results are similar to human acute self-limiting hepatitis, but adult vaccination shows transient infection. Inoculation of saplings and surrounding trees with HBV can increase the infection efficiency. Newborn trees are inoculated with human HBV, the virus will be retained in the animal body for a long time and can replicate stably. In 2012, the co-receptor-sodium ion-taurocholic acid cotransport peptide of hepatitis B virus and hepatitis D virus was found in Tupai’s primary hepatocytes, which is expected to make Tupai a reliable animal model of human HBV .

　　DHBV post-DHBV viremia in ducks is related to the age of the ducks. The timing of DHBV infection is an important factor affecting the infection rate and prognosis. After intraperitoneal injection of DHBV into 1-day-old ducks, the positive rate was about 89% after 2 weeks, and about 94% after 4 weeks, for 22 weeks. At 10 days after infection, the positive rate was only about 16% after 2 weeks, about 38% after 4 weeks, and 61.1% after 6 weeks. After 12 weeks, about half of DHBV-positive ducks showed transfection of DHBsA9 and DHBV DNA. ..shadow. The duck model has a high DHBV infection rate and is easy to raise. It is a suitable model for evaluating the effects of preclinical antiviral drugs. However, there are significant differences in the structure of DFBV avian hepatitis virus and human HBV. Ducks are evolutionarily different from humans, so they cannot replicate the human HBV infection process well.

　　WHV infection is mainly a chronic infection of neonatal woodchucks, which can be used to study the chronic mechanism of HBV, the development of HBV vaccines and antiviral drugs, and the life cycle of HBV, molecular mechanisms, infection and carcinogenesis. mechanism. However, animal models of woodchuck hepatitis virus cannot be directly infected with HBV. There are still some differences between WHV and HBV, which cannot fully simulate the pathological process of HBV.

　　Fluid mechanical transfection mouse model: This model studies the life history of HBV, the mechanism of chronic infection, especially the identification of mutant HBV-DNA and the mechanism of action of single or multiple genes in the process of HBV infection. Used for learning. It is a kind of immune all-round mice, which can be used to study the mechanism of immune effects caused by viruses.