Dataset Information

Rabbit as a novel animal model for hepatitis E virus infection and vaccine evaluation.

ABSTRACT:

Background

The identification of hepatitis E virus (HEV) from rabbits motivated us to assess the possibility of using rabbits as a non-human primate animal model for HEV infection and vaccine evaluation.

Methodology/principal findings

First, 75 rabbits were inoculated with seven strains of genotypes 1, 3, 4, and rabbit HEV, to determine the appropriate strain, administrative route and viral dosage. Second, 15 rabbits were randomly divided into three groups and vaccinated with 0 µg (placebo), 10 µg and 20 µg of HEV candidate vaccine, HEV p179, respectively. After three doses of the vaccination, the rabbits were challenged with 3.3×10(5) genome equivalents of genotype 4 HEV strain H4-NJ703. The strain of genotype 1 HEV was not found to be infectious for rabbits. However, approximately 80% of the animals were infected by two rabbit HEV strains. All rabbits inoculated with a genotype 3 strain were seroconverted but did not show viremia or fecal viral shedding. Although two genotype 4 strains, H4-NJ153 and H4-NJ112, only resulted in part of rabbits infected, another strain of genotype 4, H4-NJ703, had an infection rate of 100% (five out of five) when administrated intravenously. However, only two out of fifteen rabbits showed virus excretion and seroconversion when inoculated orally with H4-NJ703 of three different dosages. In the vaccine evaluation study, rabbits vaccinated with 20 µg of the HEV p179 produced anti-HEV with titers of 1?10(4)-1?10(5) and were completely protected from infection. Rabbits vaccinated with 10 µg produced anti-HEV with titers of 1?10(3)-1?10(4) and were protected from hepatitis, but two out of the five rabbits showed virus shedding.

Conclusions/significance

Rabbits may be served as an alternative to the non-human primate models for HEV infection and vaccine evaluation when certain virus strains, appropriate viral dosages, and the intravenous route of inoculation are selected.

SUBMITTER: Cheng X

PROVIDER: S-EPMC3521758 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

Rabbit as a novel animal model for hepatitis E virus infection and vaccine evaluation.

Cheng Xianfeng X Wang Song S Dai Xing X Shi Chengbo C Wen Yufeng Y Zhu Ming M Zhan Shenwei S Meng Jihong J

PloS one 20121213 12

<h4>Background</h4>The identification of hepatitis E virus (HEV) from rabbits motivated us to assess the possibility of using rabbits as a non-human primate animal model for HEV infection and vaccine evaluation.<h4>Methodology/principal findings</h4>First, 75 rabbits were inoculated with seven strains of genotypes 1, 3, 4, and rabbit HEV, to determine the appropriate strain, administrative route and viral dosage. Second, 15 rabbits were randomly divided into three groups and vaccinated with 0 µg ...[more]

PMID: 23272124

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Project description:Hepatitis E virus (HEV) is a viral pathogen transmitted by the fecal-oral route and is a major cause of waterborne acute hepatitis in many developing countries. In addition to infecting humans, HEV has been identified in swine, wild boars, rabbits and other mammals; with swine and wild boars being main reservoirs for zoonotic transmission of HEV. There are four major HEV genotypes known to infect humans; genotypes 1 (HEV-1) and 2 (HEV-2) are restricted to humans, and genotypes 3 (HEV-3) and 4 (HEV-4) are zoonotic. Herein, three human HEV strains originating in France were sequenced and near full-length genomes were characterized. Phylogenetic analysis showed that two strains were genotype 3 and closely grouped (a 100% bootstrap value) with subtype 3i reference strains. In percent nucleotide identities, these two strains were 94% identical to each other, 90-93% identical to subtype 3i strains, 82-86% identical to other HEV-3, and 77-79% identical to rabbit HEV strains excluding the two divergent strains KJ013414 and KJ013415 (74%); these two strains were less than 77% identical to strains of HEV genotypes 1, 2 and 4. The third strain was found distinct from any known HEV strains in the database, and located between the clusters of HEV-3 and rabbit HEV strains. This unique strain was 74-75% identical to HEV-1, 73% to HEV-2, 81-82% to HEV-3, 77-79% to rabbit HEV again excluding the two divergent strains KJ013414 and KJ013415 (74%), and 74-75% to HEV-4, suggesting a novel unclassified strain associated with HEV-3 and rabbit HEV. SimPlot and BootScan analyses revealed a putative recombination of HEV-3 and rabbit HEV sequences at four breakpoints. Phylogenetic trees of the five fragments of the genome confirmed the presence of two HEV-3 derived and three unclassified sequences. Analyses of the amino acid sequences of the three open reading frames (ORF1-3) encoded proteins of these three novel strains showed that some amino acid residues specific to rabbit HEV strains were found solely in this unclassified strain but not in the two newly identified genotype 3i strains. The results obtained by SimPlots, BootScans, phylogenetic analyses, and amino acid sequence comparisons in this study all together appear to suggest that this novel unclassified strain is likely carrying a mosaic genome derived from HEV-3 and rabbit HEV sequences, and is thus designated as a putative genotype 3/rabbit HEV recombinant.

Dataset Information

Rabbit as a novel animal model for hepatitis E virus infection and vaccine evaluation.

Background

Methodology/principal findings

Conclusions/significance

Publications

Rabbit as a novel animal model for hepatitis E virus infection and vaccine evaluation.

Similar Datasets

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