An overview: Rabbit hepatitis E virus (HEV) and rabbit providing an animal model for HEV study

Abstract

SummaryHepatitis E virus (HEV) is a single-stranded, positive-sense RNA virus and the causative agent of hepatitis E. The virus belongs to genus Orthohepevirus in the family Hepeviridae, which contains 4 major genotypes closely relating to humans. Genotypes 1 and 2 only infect humans whereas genotypes 3 and 4 HEV are harbored in a wide range of animal species worldwide and are zoonotic to humans. Recently, a novel animal strain of HEV has been isolated in farmed rabbits in China, and subsequently more strains were discovered in the rabbit populations in at least 7 other countries. Due to high sequence similarity to genotype 3 HEV, rabbit HEV (rHEV) has been assigned to genotype 3. Experimental study showed that rHEV could infect non-human primate and human, which pose a direct threat to human. Further pathogenesis studies showed laboratory rabbits infected with rHEV and genotype 4 HEV could present similar signs of acute and chronic hepatitis E along with extra-hepatic replication as observed in humans. High mortality and vertical transmission were reproduced in rHEV infected pregnant rabbits. Furthermore, rabbit model was also found suitable for evaluating HEV vaccine efficacy in order to manage zoonotic transmission. These data showed laboratory rabbits could serve as an alternative animal model for HEV study under the current circumstances that HEV propagation is limited in vitro. In general, this review aims at presenting comprehensive up-to-date information about rHEV strains and rabbit model for HEV studies.

Identification of a putative novel genotype 3/rabbit hepatitis E virus (HEV) recombinant

“…To better classify these three new strains, a phylogenetic analysis was performed. As based on the HEV reference sequences proposed by Smith et al [ 15 ] and used by others [ 28 , 29 , 33 , 35 ], 81 complete genomes of Orthohepevirus A species were retrieved from the GenBank database ( S2 Table ), including 11 HEV-1, 1 HEV-2, 22 HEV-3, 22 rabbit HEV, 17 HEV-4, 1 HEV-5, 2 HEV-6, 2 HEV-7, and 3 HEV-8 strains. A phylogenetic tree was constructed using the 81 reference sequences and the genomes of DLS13-11677, DLS13-11681, and DLS13-11685 ( Fig 1 ).…”

“…Rabbit HEV strains have been found in farmed, wild, pet and laboratory rabbits in China [ 19 , 20 ], the United States [ 21 , 22 ], France [ 23 , 24 ], Italy [ 25 , 26 ], Germany [ 27 , 28 , 29 ], the Netherlands [ 30 ], Korea [ 31 ], and Canada [ 32 ]. Phylogenetic analysis of full-length genomic sequences indicates that all rabbit HEV strains together form a separated clade that is closely related to HEV-3 (76–79% nucleotide identities, excluding the two highly divergent rabbit-derived sequences KJ013414 and KJ013415 with only 72–73% identities), but distant from other genotypes of HEV [ 33 ]. The genomes of all rabbit HEV strains harbor a signature insertion of 93-nucleotides (nt) (31 amino acids) in the X domain of ORF1 that is absent in any other known HEV strains [ 34 ].…”

Characterization of Three Novel Linear Neutralizing B-Cell Epitopes in the Capsid Protein of Swine Hepatitis E Virus

“…Previously, rabbits had been shown to be susceptible to experimental infection by genotype 4 HEV isolates from human and pig animal hosts. Moreover, the advantages of rabbits as an animal model for researching HEV pathogenicity have been described previously (46,47) and include lower cost and easier manipulation than with large animals, prompting the use of rabbits here for in vivo MAb neutralization assays. Notably, our results demonstrated that CHN-SD-sHEV (genotype 4 swine HEV) could cause robust infection of rabbits.…”

Hepatitis E virus is likely circulating in wild rabbits from Iberian Peninsula

“…Indeed, RNA levels might be below the threshold of detection limit of the PCR (see, for example, Germer et al, 2017). Moreover, HEV RNA detection rates are usually lower than those based on anti-HEV antibodies (Wang et al, 2018), making it fairly difficult to identify its circulation, even in large sample sets (e.g. Hammerschmidt et al, 2017;Izopet et al, 2012;Zhao et al, 2009).…”