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

Area of Science:

• Hepatology
• Virology
• Immunology

Background:

• Hepatitis E virus (HEV) is a leading cause of viral hepatitis worldwide.
• Studying HEV in vivo has been challenging due to the absence of effective small animal models.
• HEV is an emerging pathogen in developed nations.

Purpose of the Study:

• To establish and utilize a human liver chimeric mouse model for HEV research.
• To investigate HEV infection kinetics, viral markers, and host-pathogen interactions.
• To evaluate potential anti-HEV therapeutic strategies.

Main Methods:

• HEV infection was established in human liver chimeric mice using stool-derived HEV genotypes 1 and 3.
• Viral load and HEV antigen (Ag) levels were monitored as indicators of active infection.
• Characterization of HEV particles, HEV ORF2 Ag, and hepatic innate transcriptome was performed.

Main Results:

• Humanized mice successfully modeled chronic HEV infection, with increased viral load and HEV Ag.
• Plasma-derived HEV showed reduced infectivity compared to stool preparations.
• The model allowed for detailed study of HEV ORF2 Ag kinetics and its diagnostic implications.

Conclusions:

• Human liver chimeric mice represent a significant advancement for in vivo HEV research.
• This model facilitates the study of HEV's life cycle, host interactions, and therapeutic interventions.
• It provides a platform for understanding HEV pathogenesis and developing diagnostic and treatment strategies.