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Transmission of hepatitis E virus infection to human-liver chimeric FRG mice using patient plasma

机译:使用患者等离子体对乙型肝炎病毒感染对人肝嵌合FRG小鼠的传播

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Hepatitis E virus (HEV) is considered as an important pathogen in developing countries but there is growing evidence of its increasing significance and prevalence in the Western world. Although most acute HEV infections resolve spontaneously, chronicity has been observed in immunocompromised patients. The study of HEV has been hampered by the absence of practical animal models. Because the in vivo study of HEV was essentially limited to primates and pigs we recently established the human-liver chimeric uPA-SCID mouse model as a useful tool to study HEV infection. Because the humanized FRG mouse model, another type of mouse with humanized liver, is more easily accessible to the scientific community, we investigated its susceptibility to HEV infection. FRG mice were transplanted with human hepatocytes and challenged with different HEV genotypes using different routes of exposure. Our data clearly shows that the humanized FRG mouse is an alternative animal model for the study HEV infection. As observed in the uPA-SCID model, controlled oral inoculation did not lead to active infection. However, intrasplenic injection of genotype 3-infected patient plasma did result into persistent infection. Although the efficiency of transmission was low, this observation corroborates previously published case reports of blood transfusion-associated HEV transmission. (C) 2017 Elsevier B.V. All rights reserved.
机译:乙型肝炎病毒(HEV)被认为是发展中国家的重要病原体,但在西方世界的显着性和普遍性增加了越来越多的证据。虽然大多数急性HEV感染自发地解决,但在免疫疗效患者中观察到慢性。缺乏实用的动物模型,HEV的研究受到了阻碍。由于HEV的体内研究基本上限于灵长类动物和猪,我们最近将人肝嵌合UPA-SCID小鼠模型作为研究HEV感染的有用工具。由于人源化的FRG小鼠模型,另一种类型的小鼠与人源化肝脏,更容易对科学界进行的,我们调查了对HEV感染的易感性。将FRG小鼠移植用人肝细胞,并用不同的暴露途径用不同的HEV基因型攻击。我们的数据清楚地表明,人性化FRG鼠标是研究HEV感染的替代动物模型。如在UPA-SCID模型中所观察到的,受控口腔接种不会导致活性感染。然而,肾包翻钙注射基因型3感染的患者血浆确实导致持续的感染。虽然透射效率低,但这种观察结果证实了先前公布的血液输血相关HEV传输的病例报告。 (c)2017 Elsevier B.v.保留所有权利。

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