In vivo models for studying Hepatitis E virus infection; Updates and applications

Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis globally. HEV belongs to the Hepeviridae family and at least five genotypes (gt) infect humans. Several animal species are reservoirs for different HEV strains, and they are the source of infection for humans. Some HEV strains are species specific, but other strains could cross species and infect many hosts. The study of HEV infection and pathogenesis was hampered due to the lack of an in vitro and in vivo robust model system. The cell culture system has been established for certain HEV strains, especially gt3 and 4, but gt1 strains replicate poorly in vitro. To date, animal models are the best tool for studying HEV infection. Non-human primates (NHPs) and pigs are the main animal models used for studying HEV infection, but ethical and financial concerns restrict the use of NHPs in research. Therefore, new small animal models have been developed which help more progress in HEV research. In this review, we give updates on the animal models used for studying HEV infection, focusing on the applicability of each model in studying different HEV infections, cross-species infection, virus-host interaction, evaluation of anti-HEV therapies and testing potential HEV vaccines.