疾病动物模型,导丙型肝炎病毒动物模型 z-bio 2021-03-10 524

　　The natural host of HCV infection is limited to humans and chimpanzees. The establishment of an ideal experimental infection model is the key to studying the carcinogenic effects of persistent HCV infection, drug screening and vaccine evaluation. The currently used HCV animal models mainly include chimpanzee hepatitis C model, tree sh hepatitis C model and rat hepatitis C model.

　　[Modeling mechanism] The infection route of hepatitis C virus is the same as that of HIV and hepatitis B virus, mainly blood transfusion, mother-to-child transmission and sexually transmitted infection. Animals are intravenously injected with HCV patient serum or HCVcc in cell culture. This is the disease process after humans are naturally infected with hepatitis C virus.

　　[Modeling method] Chimpanzee (pan-chimpanzee): Use blood products from HCV patients to inject the chimpanzee intravenously, or inject HCVNA prepared by in vitro transcription into the liver of the chimpanzee. This may cause chimpanzees to be infected with the HCV virus. Chimpanzees were infected with HCV, transaminase was elevated, and liver biopsy showed acute necrotizing inflammatory changes.

　　Tupai: HCV virus (HCVcc) obtained from the serum or cell culture of HCV patients is injected into Tupai by intravenous or hepatic multi-point injection. This may infect sh trees with HCV and cause intermittent viremia. Rats: Human primary hepatocytes or human liver cancer Huh7 are intraperitoneally injected into fetal mice with a gestational age of 15 to 17 days, and human primary hepatocytes or Huh7 are transplanted within 24 hours after birth to produce fetal mice. After the immune system acquires immune tolerance, HCV is isolated from the patient's serum after infecting these cells during development. This can lead to HCV infection.

　　[Model Features] Chimpanzees are the natural host of HCV. When infected with HCV, the virus clears naturally. Chronic carriers will not develop liver cirrhosis or liver fibrosis, and are ineffective in treating interferon. According to reports, few chimpanzees eventually develop hepatocellular carcinoma after being infected with HCV. infection

　　HCV tree can can cause transient viremia and is positive for HCV antibodies, ALT and HCVNA. The plasma of positive trees can also be used for new trees infected with HCV. The pathological changes of liver tissue of trees infected with HCV are consistent with the progress of human hepatitis C. That is, chronic hepatitis→hepatic steatosis→cirrhosis. → Liver cancer. Figure 7-1 / Figure 7-1 at the end of the color text shows the pathological changes in the liver of a tree infected with HCV. Four weeks after HCV infection, 7.0 x 1000 copies/ml HCVNA can be detected in rat serum. After 12 weeks, HCVNA reached a peak of 20 x 1000 copies/ml and then began to decline. Alanine aminotransferase began to increase in the 4th week, reached high levels in the 13th week, and then began to decrease. Under the microscope, the infiltration of monocytes can be seen in the door and the middle.

　　[Model Evaluation and Application] Currently, chimpanzees are the only primates other than humans to be infected with HCV. Chimpanzees are infected with HCV. The clinical course of chimpanzees is similar to that of human HCV infection and can form chronic infections. There will be no chronic carriers. It is specially developed for liver cirrhosis or liver fibrosis. It can be used to study the acute infection of HCV, the virological changes of HCV and the immune response of the host in the acute phase, as well as the natural infection of HCV and the changes of pathology and immune response during the development of HCV vaccine. .. However, chimpanzees are not suitable for studying chronic infections or hepatocellular carcinoma associated with HCV. IH currently prohibits the use of chimpanzees in biomedical research. Treeshrew is a promising animal model of HCV, genetically and evolutionarily closer to primates than mice and rabbits. After being infected with HCV, transient viremia may occur, and it is positive for HCV antibodies, ALT and HCVNA. It can be used to study the mechanism of HCV invasion and replication. From

　　The animals obtained from the rat model are rats with normal immune function and can be used as tools for HCV infiltration, replication, immune liver injury research and drug screening. However, due to the limited number of humans, hepatocellular carcinoma is transplanted into the body and the low viral load after HCV infection also limits its application.