ABSTRACT
Objective The hepatitis E virus (HEV) is responsible for
approximately 20 million infections per year worldwide.
Although most infected people can spontaneously clear
an HEV infection, immune-compromised individuals may
evolve towards chronicity. Chronic HEV infection can be
cured using ribavirin, but viral isolates with low ribavirin
sensitivity have recently been identified. Although some
HEV isolates can be cultured in vitro, in vivo studies are
essentially limited to primates and pigs. Since the use of
these animals is hampered by financial, practical and/or
ethical concerns, we evaluated if human liver chimeric
mice could serve as an alternative.
Design Humanised mice were inoculated with different
HEV-containing preparations.
Results Chronic HEV infection was observed after
intrasplenic injection of cell culture-derived HEV, a
filtered chimpanzee stool suspension and a patientderived stool suspension. The viral load was significantly
higher in the stool compared with the plasma. Overall,
the viral titre in genotype 3-infected mice was lower
than that in genotype 1-infected mice. Analysis of liver
tissue of infected mice showed the presence of viral RNA
and protein, and alterations in host gene expression.
Intrasplenic injection of HEV-positive patient plasma and
oral inoculation of filtered stool suspensions did not
result in robust infection. Finally, we validated our model
for the evaluation of novel antiviral compounds against
HEV using ribavirin.
Conclusions Human liver chimeric mice can be
infected with HEV of different genotypes. This small
animal model will be a valuable tool for the in vivo
study of HEV infection and the evaluation of novel
antiviral molecules