Hepatitis A virus (HAV) is a small RNA virus that is the primary cause of acute viral hepatitis. HAV is very stable, heat- and acid-resistant, unlike other small RNA family viruses, which facilitates transmission of the virus. Hepatitis A is mainly transmitted through the fecal-oral route (digestive tract), and other routes include blood transmission and vertical transmission. The hosts of HAV are mainly limited to humans and non-human primates. However, HAV can be successfully cultured in mouse and guinea pig cells, suggesting that other types of hosts may exist. To date, animal models of HAV pathogenicity and host immune responses have been mainly in non-human primates, mainly chimpanzees and monkeys. The animal models of HAV generally used internationally include marmosets, rhesus monkeys, crab-eating monkeys, and tree shrews.

Ace Therapeutics focuses on the research of parasitic organisms and has established a technical platform for the construction of parasitic organism animal models, aiming to provide a variety of parasitic organism animal model development and customization services to customers worldwide. Among them, we can provide customization services for hepatitis A virus models, including crab-eating monkey models, tree shrew models, marmoset models, etc.

Customization Service Options for Animal Models of Hepatitis A Infection

[Modeling mechanism] Fresh stool filtrate from HAV patients was injected intravenously into the animals, or fresh stool suspension from HAV patients was gavaged into the animals.

• Hepatitis A virus crab-eating macaque model

[Model characteristics] After crab-eating macaque was infected with HAV, alanine aminotransferase (ALT) started to increase on day 7 and peaked on day 20, IgM and total HAV antibodies started to increase on day 14 and peaked on day 20, then slowly decreased. HAV nucleic acid can be detected in the feces on day 7, and the viral load reaches 10 copies/ml in the feces on day 15, 10 copies/ml in the serum on day 20, and 10 copies/ml in the saliva on day 7. HAV antigen can be consistently detected in the liver and salivary glands from day 7 to 60 of infection.

Intermediate products of HAV replication can be detected in the liver, salivary glands, tonsils, and lymph nodes, and salivary glands can be used as target organs for early extrahepatic HAV replication. Histopathological examination of the liver showed swelling of hepatocytes, and inflammatory cell infiltration was seen in the confluent area.

[Model evaluation and application] Crab-eating monkeys are closer to humans in terms of phylogeny and immune regulation than rodents, and can better visualize the immune regulation and viral replication of the human-like organism after infection, which can be used for the study of the pathogenesis of hepatitis A and the evaluation of the effectiveness of hepatitis A vaccine.

• Hepatitis A virus tree shrew model

[Model characteristics] Hepatitis A antigen can be measured in fecal extracts 7-13 days after infection, virus particles can be observed under an electron microscope, and detoxification lasts 15-21 days and basically stops after 30 days. Some tree shrews showed elevated glutamate transaminase (GPT) after infection, and antibodies to the hepatitis A virus were detected in serum 2-16 weeks after infection. Pathological examination showed varying degrees of hepatic congestion, edema, and steatosis, with the proliferation of Kupffer cells and occasional small necrotic spots of hepatic parenchymal cells.

[Transverse type evaluation and application] Hepatitis A virus can multiply in the tree shrew and detoxify continuously over a period of time. The liver of tree shrews is congested and edematous after infection. Compared with marmosets and chimpanzees, the liver lesions of tree shrews are less severe. Tree shrews are non-human primate relatives and have the advantages of being economical, easy to obtain, and having a short experimental period compared to monkeys and chimpanzees.

• Hepatitis A virus marmoset model

[Model characteristics] After the marmoset was infected with HAV, ALT increased in the second week and peaked in the fourth week, IgM increased in the third week and peaked one to two weeks later, and IgM was almost undetectable in the fifth week, but IgG levels were high. HAV antigen was detected in the stool on days 6-7, with a peak in detoxification on days 11-17 and a cessation of detoxification on days 20. Pathological examination on day 16 after infection revealed enlarged hepatocytes in the portal vein region. Electron microscopy revealed the presence of 22~27 nm diameter particles in hepatocytes and fecal extracts after immunoprecipitation. Immunohistochemistry of liver biopsies revealed fluorescent particles in hepatocytes and kupffer cytoplasm.

[Model evaluation and application] The marmoset is a relatively widely used animal model of hepatitis A internationally. The biochemical indices, pathological examination, and electron microscopy after viral infection showed the immune process of hepatitis A virus infection in marmosets, which can be used for the study of the pathogenic mechanism of hepatitis A.

Service Details

Delivery content: experiment report and HAV animal models.
Test fee: please get it through online inquiry .

• Parasitology discovery and pre-research service
• Parasitology metabolism research service
• Parasitology target and structure function research
• Parasitology effectiveness evaluation service
• Parasitology safety evaluation service
• Parasitology pharmacological research service