Animal models of hepatitis E infection: Advances and challenges

Hepatitis E virus (HEV) is one of the leading causes of acute viral hepatitis worldwide. Although most of HEV infections are asymptomatic, some patients will develop the symptoms, especially pregnant women, the elderly, and patients with preexisting liver diseases, who often experience anorexia, nausea, vomiting, malaise, abdominal pain, and jaundice. HEV infection may become chronic in immunosuppressed individuals. In addition, HEV infection can also cause several extrahepatic manifestations. HEV exists in a wide range of hosts in nature and can be transmitted across species. Hence, animals susceptible to HEV can be used as models. The establishment of animal models is of great significance for studying HEV transmission, clinical symptoms, extrahepatic manifestations, and therapeutic strategies, which will help us understand the pathogenesis, prevention, and treatment of hepatitis E. This review summarized the animal models of HEV, including pigs, monkeys, rabbits, mice, rats, and other animals. For each animal species, we provided a concise summary of the HEV genotypes that they can be infected with, the cross-species transmission pathways, as well as their role in studying extrahepatic manifestations, prevention, and treatment of HEV infection. The advantages and disadvantages of these animal models were also emphasized. This review offers new perspectives to enhance the current understanding of the research landscape surrounding HEV animal models.