Characterization of hepatitis E virus infection in tree shrew (Tupaia belangeri chinensis).

Characterization of hepatitis E virus infection in tree shrew (Tupaia belangeri chinensis).
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树鼩(Tupaia belangeri chinensis)戊型肝炎病毒感染的特征

DOI:
10.1186/s12879-016-1418-1
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发表时间:
2016-02-16
影响因子:
3.7
通讯作者:
Huang F
Huang F
中科院分区:
医学3区
文献类型:
--
作者:
Yu W;Yang C;Bi Y;Long F;Li Y;Wang J;Huang F

文献摘要

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背景:戊型肝炎病毒(HEV)是发展中国家肝炎的主要原因,对全球公共卫生构成威胁。树鼩(Tupaia belangeri chinensis)是研究肝炎病毒(例如乙型肝炎病毒和丙型肝炎病毒)的有用动物模型。然而,这种动物模型在HEV研究中的应用尚未开发。方法:对树鼩进行静脉注射(IV)猪基因型4 HEV或通过接触暴露于IV感染的树鼩进行感染。 RT-nPCR 检测粪便、组织和血液中的 HEV RNA。通过Western blot检测不同组织中的HEV衣壳蛋白,并通过定量RT-PCR估计。通过ELISA测定抗HEV抗体。通过组织病理学检查和肝脏特异性酶活性分析评估肝损伤情况。结果:接种后3-4天感染HEV或接触暴露的树鼩粪便中均检测到HEV RNA的阴性和阳性链。在肝脏、脾脏、肾脏和胆汁中可检测到 HEV RNA。所有感染 HEV 的树鼩均出现病毒血症。 HEV衣壳蛋白在肝脏、脾脏和肾脏中表达。组织学检查和肝脏特异性酶活性分析表明,HEV引起树鼩的急性肝脏病变。同时,受感染的树鼩表现出IgG和IgM抗体阳性。结论:树鼩对HEV易感,可能成为HEV实验感染研究、发病机制或临床前药物开发的有用动物模型。
Background:Hepatitis E virus (HEV) is a major cause of hepatitis in developing countries and poses a threat to public health worldwide. Tree shrew (Tupaia belangeri chinensis) is a useful animal model in studies on hepatitis viruses, such as hepatitis B and C viruses. However, the use of this animal model for HEV research is yet to be developed.Methods:Tree shrews were intravenously (IV) injected with swine genotype 4 HEV or infected by contact-exposure to IV infected tree shrews. RT-nPCR was performed to detect HEV RNA in the feces, tissues, and blood. HEV capsid protein in the different tissues was detected by Western blot and estimated by quantitative RT-PCR. Anti-HEV antibodies were determined by ELISA. Liver damages were evaluated by histopathologic examination and analysis of liver-specific enzymes activities.Results:Both negative and positive strands of HEV RNA were detected in the feces of the HEV-infected or contact-exposed tree shrews 3-4 days post-inoculation. HEV RNA was detectable in the liver, spleen, kidneys, and bile. Virusemia developed in all the HEV-infected tree shrews. HEV capsid protein was expressed in the liver, spleen, and kidneys. The histological examination and analysis of liver-specific enzymes activities showed that HEV caused acute liver lesions in the tree shrews. Meanwhile, the infected tree shrews showed positive IgG and IgM antibodies.Conclusions:Tree shrews are susceptible to HEV and may be useful animal models for HEV experimental infection studies on pathogenesis or preclinical drug development.