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Experimental Infection of Rabbits with Rabbit and Genotypes 1 and 4 Hepatitis E Viruses

Ma, HX; Zheng, L; Liu, YB; Zhao, CY; Harrison, TJ; Ma, YY; Sun, SH; ... Wang, YC; + view all (2010) Experimental Infection of Rabbits with Rabbit and Genotypes 1 and 4 Hepatitis E Viruses. PLOS ONE , 5 (2) , Article e9160. 10.1371/journal.pone.0009160. Green open access

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Abstract

Background: A recent study provided evidence that farmed rabbits in China harbor a novel hepatitis E virus (HEV) genotype. Although the rabbit HEV isolate had 77-79% nucleotide identity to the mammalian HEV genotypes 1 to 4, their genomic organization is very similar. Since rabbits are used widely experimentally, including as models of infection, we investigated whether they constitute an appropriate animal model for human HEV infection.Methods: Forty-two SPF rabbits were divided randomly into eleven groups and inoculated with six different isolates of rabbit HEV, two different doses of a second-passage rabbit HEV, and with genotype 1 and 4 HEV. Sera and feces were collected weekly after inoculation. HEV antigen, RNA, antibody and alanine aminotransferase in sera and HEV RNA in feces were detected. The liver samples were collected during necropsy subject to histopathological examination.Findings: Rabbits inoculated with rabbit HEV became infected with HEV, with viremia, fecal virus shedding and high serum levels of viral antigens, and developed hepatitis, with elevation of the liver enzyme, ALT. The severity of disease corresponded to the infectious dose (genome equivalents), with the most severe hepatic disease caused by strain GDC54-18. However, only two of nine rabbits infected with HEV genotype 4, and none infected with genotype 1, developed hepatitis although six of nine rabbits inoculated with the genotype 1 HEV and in all rabbits inoculated with the genotype 4 HEV seroconverted to be positive for anti-HEV IgG antibody by 14 weeks post-inoculation.Conclusions: These data indicate that rabbits are an appropriate model for rabbit HEV infection but are not likely to be useful for the study of human HEV. The rabbit HEV infection of rabbits may provide an appropriate parallel animal model to study HEV pathogenesis.

Type: Article
Title: Experimental Infection of Rabbits with Rabbit and Genotypes 1 and 4 Hepatitis E Viruses
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0009160
Publisher version: http://dx.doi.org//10.1371/journal.pone.0009160
Language: English
Additional information: © 2010 Ma et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This study was supported by the 863 project (grant: 2006AA02Z453) from the Ministry of Science and Technology, China. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Keywords: RT-PCR ASSAY, SWINE, HEV, SEQUENCE, PIGS, PREVALENCE, DEER, PATHOGENESIS, CHINA, TRANSMISSION
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Internal Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/72274
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