Study of hepatitis E virus infection of genotype 1 and 3 in mice with humanised liver

Abstract

Human liver chimeric mice can be infected with HEV of different genotypes. This small animal model will be a valuable tool for the study of HEV infection and the evaluation of novel antiviral molecules.

Review article: hepatitis E—a concise review of virology, epidemiology, clinical presentation and therapy

“…[31][32][33] Interestingly, these reports indicated greater success using genotype 1 strains as inoculants (in contrast to in vitro studies) and all achieved greater infection and viraemia rates in inoculated mice using faecally derived HEV virions, in comparison to serum or culture derived. Two studies examined the use of ribavirin in inoculated chimeric mice and demonstrated the treatment to be successful in reducing viraemia in therapeutics.…”

“…Two studies examined the use of ribavirin in inoculated chimeric mice and demonstrated the treatment to be successful in reducing viraemia in therapeutics. 31,33 However, ribavirin-induced anaemia was common in the treated mice (a side effect documented in humans). 31 …”

Elucidating the differences in pathogenicity between hepatitis E virus genotypes: The quest continues

“…Infection with full‐length gt1 HEV was not successful, but it remains unclear whether this is typical for gt1 viruses in JEG‐3 cells or rather due to the inherent low replicative capacity of Sar55 in cell culture; most likely it is due to the latter. Interestingly, we recently showed that Sar55 propagates more efficiently and replicates at a much higher level in immune‐deficient mice with humanized liver compared to the gt3 isolate p6,7 highlighting the difference in gt1 HEV replication in vivo and in vitro .…”

“…Ribavirin (RBV), a broad‐spectrum antiviral with proven activity against HEV in cell culture, preclinical animal models, and in patients (but unfortunately contraindicated during pregnancy),1, 2, 7, 8 also effectively inhibited HEV replication in JEG‐3 cells, thereby validating this cell culture model for the discovery of novel direct antiviral agents. The added value of sofosbuvir in this context is questionable.…”

Un modèle murin pour une infection chronique méconnue : l’hépatite E !

“…Des atteintes extrahé-patiques, dont le mécanisme sous-jacent n'est pour l'instant pas compris, sont éga-lement rapportées. additif à celui de la ribavirine, sur la réplication du VHE in vitro [6] [7][8][9]. Les auteurs ont utilisé un modèle classique de repeuplement du foie de souris immunosupprimées par des hépatocytes humains (Figure 1).…”