Updates in Hepatitis E virus (HEV) field; lessons learned from human liver chimeric mice.

Hepatitis E virus (HEV) is the most common cause of viral hepatitis globally, and it is an emerging pathogen in developed countries. In vivo studies of HEV have long been hindered due to the lack of an efficient small animal model. Recently, human liver chimeric mice were described as an elegant model to study chronic HEV infection. HEV infection was established in mice with humanized liver that were challenged with stool preparations containing HEV genotype (gt)1 and/or gt3. An increase in viral load and the level of HEV Ag in mouse samples were markers of active infection. Plasma-derived HEV preparations were less infectious. The kinetics of HEV ORF2 Ag during HEV infection and its impact on HEV diagnosis were described in this model. In addition, the nature of HEV particles and HEV ORF2 Ag were characterized. Moreover, humanized mice were used to study the impact of HEV infection on the hepatic innate transcriptome and evaluation of anti-HEV therapies. This review highlights recent advances in the HEV field gathered from well-established experimental mouse models, with an emphasis on this model as a tool for elucidating the course of HEV infection, the study of the HEV life cycle, the interaction of the virus with the host, and the evaluation of new anti-HEV therapies.