3 ǀ HEV ANIMAL MODELS
In vivo studies on HEV infection have long been hindered due to many issues such as the lack of a small animal model. Recently, to study the HEV infection human liver chimeric mice were used.85 For some HEV strains, the cell culture system has been established such as genotype 3, genotype 4, and genotype 1, among these genotypes the genotype 1 replicate poorly in vitrosystem. The best animal models to study HEV infection are pigs and non-human primates (NHPs) such as African green monkeys, chimpanzees, cynomolgus monkey, owl monkeys, squirrel monkeys, rhesus macaques, vervets, tamarins, but some issues like finance and research ethics restrict the use of these models in research. Therefore, much attention has been paid to the development of small animal models to study the HEV infection properly, examine cross-species transmission, elucidate virus and host interaction, testing the potential and efficacy of HEV vaccines, and analyze adverse outcomes.86
From pregnant mice tissues (liver, spleen, kidney, colon, uterus, and placenta), the establishment of the HEV infection was confirmed by detection of HEV RNA. The results showed that the HEV infection was successfully established with a high rate of miscarriage (7/8, 87.5%) in the middle of pregnancy. To study the HEV infection in pregnant women, this animal model can be used to study the HEV adverse outcomes, pathogenesis, and host response. This model may be useful for future anti-HEV drug development.87