Animal Models for Hepatitis E virus

Abstract

Hepatitis E virus (HEV) is an underdiagnosed pathogen with approximately 20 million infections each year and currently the most common cause of acute viral hepatitis. HEV was long considered to be confined to developing countries but there is increasing evidence that it is also a medical problem in the Western world. HEV that infects humans belongs to the Orthohepevirus A species of the Hepeviridae family. Novel HEV-like viruses have been observed in a variety of animals and some have been shown to be able to cross the species barrier, causing infection in humans. Several cell culture models for HEV have been established in the past years, but their efficiency is usually relatively low. With the circulation of this virus and related viruses in a variety of species, several different animal models have been developed. In this review, we give an overview of these animal models, indicate their main characteristics, and highlight how they may contribute to our understanding of the basic aspects of the viral life cycle and cross-species infection, the study of pathogenesis, and the evaluation of novel preventative and therapeutic strategies.

Keywords: Hepatitis E virus; animal model; cross-species infection; pathogenicity; vaccine; zoonosis.

Figure 1

Successful experimental cross-species infections. A variety of human genotypes have been shown to cross the species barrier and infect human liver chimeric mice, gerbils, pigs, macaques, and chimpanzees. Genotype 3 and 4 isolated from pigs can cause infection in the non-human primate models, whereas BALB/c nude mice, gerbils, and rabbits were only susceptible to genotype 4 swine HEV. Rabbit HEV can replicated in pigs, BALB/c nude mice, and cynomolgus macaques, and rabbits themselves are prone to wild-boar derived genotype 3 HEV. Camel genotype 8 HEV and wild boar derived genotype 5 can infect cynomolgus macaques.