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兔3型戊型肝炎病毒(HEV-3)与人源HEV-3(JRC-HE3)在无特定病原体(SPF)兔中的不同易感性及发病机制

Different susceptibility and pathogenesis of rabbit genotype 3 hepatitis E virus (HEV-3) and human HEV-3 (JRC-HE3) in SPF rabbits.

作者信息

Zhang Yulin, Gong Wanyun, Song William Tianshi, Fu Hongwei, Wang Lin, Li Manyu, Wang Ling, Zhuang Hui

机构信息

Department of Microbiology and Center of Infectious Disease, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.

School of Laboratory Medicine, Tianjin Medical University, Tianjin, 300203, China.

出版信息

Vet Microbiol. 2017 Aug;207:1-6. doi: 10.1016/j.vetmic.2017.05.019. Epub 2017 May 29.

DOI:10.1016/j.vetmic.2017.05.019
PMID:28757007
Abstract

Hepatitis E virus (HEV) is an increasingly important zoonotic infection in humans with HEV genotypes 3 and 4 being recognized as zoonotic pathogens. The relatively recently isolated genotype 3 rabbit HEV (rHEV-3) and the more well known genotype 3 isolates from humans and swine (hsHEV-3) have all been confirmed experimentally to be capable of infecting both non-human primates and specific-pathogen free (SPF) pigs. In a previous study rHEV-3 was shown to cause acute hepatitis in experimentally infected rabbits. However, whether hsHEV-3 can productively infect rabbits remained unclear. The objective of this study was to investigate the experimental infection of rabbits with human HEV-3 (hHEV-3, JRC-HE3), to compare it to that with rHEV-3 (CHN-BJ-rb14) and to further characterise the pathogenesis of the two isolates. All animals inoculated with rHEV-3 (CHN-BJ-rb14) became infected, exhibiting an intermittent viremia, elevated liver enzymes, and persistent fecal virus shedding throughout the 15 week study period. Liver histopathology showed acute inflammation and both positive- and negative-stranded viral RNA was detected in various tissues from necropsied rabbits. By contrast, neither sero-conversion nor alanine aminotransferase (ALT) elevation was observed in most rabbits inoculated with hHEV-3 (JRC-HE3). In addition, rHEV-3 (CHN-BJ-rb14) but not hHEV-3 (JRC-HE3) recovered from primary infected rabbits was transmissible to naive rabbits. These results showed that SPF rabbits are readily susceptible to infection with rHEV-3 (CHN-BJ-rb14) but not hHEV-3 (JRC-HE3), which might indicate the influence of viral genomic organization on its pathogenicity.

摘要

戊型肝炎病毒(HEV)在人类中是一种日益重要的人畜共患感染源,其中HEV 3型和4型被认为是动物源性病原体。相对较新分离出的3型兔戊型肝炎病毒(rHEV-3)以及更为人熟知的来自人类和猪的3型分离株(hsHEV-3),均已通过实验证实能够感染非人灵长类动物和无特定病原体(SPF)猪。在先前的一项研究中,rHEV-3被证明可在实验感染的兔子中引发急性肝炎。然而,hsHEV-3是否能有效感染兔子仍不清楚。本研究的目的是调查兔子经人源HEV-3(hHEV-3,JRC-HE3)的实验性感染情况,将其与经rHEV-3(CHN-BJ-rb14)的感染情况进行比较,并进一步阐明这两种分离株的发病机制。所有接种rHEV-3(CHN-BJ-rb14)的动物均被感染,在整个15周的研究期间呈现间歇性病毒血症、肝酶升高以及持续性粪便病毒排出。肝脏组织病理学显示有急性炎症,并且在尸检兔子的各种组织中均检测到正链和负链病毒RNA。相比之下,大多数接种hHEV-3(JRC-HE3)的兔子既未出现血清转化,也未观察到丙氨酸氨基转移酶(ALT)升高。此外,从初次感染兔子中分离出的rHEV-3(CHN-BJ-rb14)可传播给未感染的兔子,而hHEV-3(JRC-HE3)则不能。这些结果表明,SPF兔子对rHEV-3(CHN-BJ-rb14)感染易感,而对hHEV-3(JRC-HE3)不易感,这可能表明病毒基因组结构对其致病性有影响。

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