Customized Services for Animal Model of Hepatitis C Infection
Hepatitis C is now an important cause of liver cancer and cirrhosis, and treatment and research on hepatitis C are urgently needed, and a stable and reliable animal model of infection would be helpful in the study of treatment of hepatitis C. Research on the treatment of hepatitis C virus infection has been hampered by the lack of a small animal model of the disease, probably due to the selective susceptibility of primates to infection. Current research has focused on how the hepatitis C virus enters, reproduces, and spreads in animals, particularly on the mechanism of hepatitis C virus infection. Some progress has been made in the study of hepatitis C virus infection in chimpanzees, mice, and rats.
The natural hosts of HCV infection are limited to humans and chimpanzees, and the establishment of ideal experimental infection models has become critical for the study of HCV persistent infection for carcinogenesis, drug screening, and vaccine evaluation. Currently, the main animal models of HCV are chimpanzees, tree shrews, rats, and mice.
Ace Therapeutics can provide customization services for hepatitis C virus models. A variety of custom HCV models are currently available, including chimpanzee, tree shrew, rat, and mouse HCV models. These models can be used to study HCV persistent infection as a key to carcinogenesis, drug screening, and vaccine evaluation.
Customization Service Options for Animal Models of Hepatitis C Infection
[Modelling mechanism] Hepatitis C virus is transmitted mainly via blood transfusion, mother-to-child, and sexual transmission, and the intravenous injection of HCV patient serum or cell culture HCVcc into animals induces a disease process similar to that seen in humans after natural infection with the hepatitis C virus.
- Chimpanzees model of Hepatitis C
[Modeling method] Chimpanzees can be infected with the HCV virus by intravenous injection of blood products from HCV patients or by injecting HCV RNA prepared by in vitro transcription into the liver of chimpanzees.
[Model characteristics] Chimpanzees are natural hosts of HCV and develop elevated transaminases after HCV infection and can clear the virus naturally. Chronic carriers do not develop cirrhosis or liver fibrosis and are ineffective in interferon therapy. Only a few chimpanzees infected with HCV have been reported to eventually develop hepatocellular liver cancer.
[Model evaluation and application] Chimpanzees are the only primates other than humans that can be infected by HCV. The clinical course of HCV infection in chimpanzees is similar to that of HCV infection in humans and is capable of developing a chronic infection, and chronic carriers do not develop cirrhosis or liver fibrosis. It can be used to study the acute infection of HCV and to study the virological changes of HCV and the immune response of the host during the acute period. To study the changes in pathology and immune response during natural infection with HCV and the development of HCV vaccines. However, chimpanzees are not suitable for studying chronic infections and hepatocellular liver cancer associated with HCV.
- Tree shrew model of Hepatitis C
[Modeling method] We infected tree shrews with HCV and developed intermittent viremia by injecting the HCV virus obtained from HCV patient serum or cell culture into tree shrews via intravenous/liver injection.
[Model characteristics] Tree shrews infected with HCV can produce transient viremia with positive HCV antibodies, ALT, and HCV RNA. Plasma from positive tree shrews can also infect new tree shrews. The course of liver histopathological changes after HCV infection in tree shrews is consistent with the progression of hepatitis C in humans, i.e., chronic hepatitis, hepatic steatosis, cirrhosis, and hepatocellular carcinoma.
[Model evaluation and application] Tree shrews are a promising animal model for HCV, genetically and evolutionarily closer to primates than mice and rabbits. Infection with HCV produces transient viremia and positivity for HCV antibodies, ALT, and HCV RNA. It can be used to study the mechanism of HCV invasion and replication.
[Modeling method] We injected human primary hepatocytes or human hepatoma cells Huh7 intraperitoneally into fetal rats at a gestational age of 15-17 days and transplanted human primary hepatocytes or Huh7 into them within 24 hours of birth, so that the immune system of the fetal rats acquired immune tolerance to these cells during development, and subsequently inoculated the rats with HCV isolated from patient serum, which could cause them to acquire infectivity to HCV.
[Model characteristics] In rats, 7.0×1000 copies/ml HCV RNA was detectable in serum after 4 weeks of HCV infection, and HCV RNA reached a peak of 20×1000 copies/ml after 12 weeks, after which it began to decline. Alanine aminotransferase began to rise at 4 weeks, reached a high bee at week 13, and then began to decline. Mononuclear cell infiltration in the hilar and central regions of the liver was seen microscopically.
[Model evaluation and application] The rat model was obtained from immunocompetent rats and can be used to study HCV invasion, replication, and immune-mediated liver injury and as a tool for drug screening.
- Transgenic mouse model of Hepatitis C
[Modeling method] The gene to be transferred (HCV 5' UTR with structural genes (C1 + E1 + E2)) was injected into the male anterior nucleus of mouse fertilized eggs by microinjection in an amount of 1 to 2 pl/egg, and then transplanted into the oviducts of 6-week-old pseudopregnant females with about 20 oviducts on each side and left to develop and give birth to litters.
[Model characteristics] In mice expressing the HCV nonstructural protein Ns5A gene, no hepatic histopathology or direct cellular pathogenicity was observed. The most striking manifestation in transgenic mice expressing HCV core protein was the induction of hepatic fatty changes and hepatocellular carcinogenesis, which is also seen in many chronic HCV infections. Lipid peroxidation and mitochondrial DNA damage due to increased reactive oxygen species were also observed in mice transgenic for HCV core protein, suggesting that the appearance of hepatocellular carcinogenesis may be related to increased reactive oxygen species and consequently DNA damage. Also, hepatic steatosis and hepatocellular carcinogenesis were observed in a trans-structured gene (Core/E1/E2/P7) and a mouse strain transduced with an intact HCV ORF.
[Model evaluation and application] The transgenic mouse system is considered to be the best system to study the regulation of gene expression, which can explore the gene activity pattern and its phenotypic effects from both spatial and temporal perspectives. the establishment of the HCV structural gene mouse model provides an important technical guarantee for the establishment of the HCV whole gene transgenic mouse model and its use to study the mechanism of HCV infection cells, the assembly and intracellular transport of HCV virulent strains in hepatocytes, the HCV gene The establishment of the HCV full gene transgenic mouse model and its use to study the mechanism of HCV infection, the assembly and intracellular transport of HCV virulent strains in hepatocytes, the virulence of HCV gene replication in hepatocytes, and the immunopathology of HCV structural proteins in the liver provide important technical assurance.
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