Experimental Transmission of Equine Hepacivirus in Horses as a Model for Hepatitis C Virus
Experimental Transmission of Equine Hepacivirus in Horses as a Model for Hepatitis C Virus
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DOI：
10.1002/hep.27689
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发表时间：
2015-05-01
期刊：
影响因子：
13.5
通讯作者：
Mealey, Robert H.
中科院分区：
文献类型：
--
作者：
Ramsay, Joshua D.;Evanoff, Ryan;Mealey, Robert H.
马肝炎病毒（EHCV; nonprimate hepacivirus）是黄病毒科的嗜肝成员，感染马。虽然EHCV是已知的与丙型肝炎病毒（HCV）最接近的病毒，但其完整的体内复制动力学尚未被描述，并且缺乏其导致肝炎的直接证据。在这项研究中，我们检测到EHCV在2匹马发生输血后肝炎。这些马的血浆和血清用于实验性传播EHCV到4个年轻的成年阿拉伯马，两个1个月大的马驹（1个阿拉伯和1个阿拉伯小马交叉），和2个马驹（1个阿拉伯和1个阿拉伯小马交叉）与严重联合免疫缺陷（SCID）。我们的研究结果表明，EHCV的感染动力学与HCV相似，感染与急性和慢性肝脏疾病相关，通过肝脏特异性酶升高和/或组织病理学测定。虽然这些动物中的大多数都与马佩吉病毒（EPgV），也是一种黄病毒，EPgV病毒载量低得多，往往在肝脏和血液中检测不到。然后用仅含EHCV的血浆接种另外三只年轻成年阿拉伯矮种马和1只SCID马驹，观察到轻度肝细胞损伤的证据。在EHCV感染期间观察到的不同水平的肝脏特异性酶升高、肝脏炎症和病毒血症持续时间表明，肝脏疾病的程度和病程是由病毒接种物和/或宿主因素介导的，包括品种、年龄和适应性免疫状态。结论：这项工作文件的完整感染动力学和肝脏病理学与急性和慢性EHCV感染的马，并进一步证明它作为一个大型动物模型的HCV。（肝病学2015;61：1533-1546）
Equine hepacivirus (EHCV; nonprimate hepacivirus) is a hepatotropic member of the Flaviviridae family that infects horses. Although EHCV is the closest known relative to hepatitis C virus (HCV), its complete replication kinetics in vivo have not been described, and direct evidence that it causes hepatitis has been lacking. In this study, we detected EHCV in 2 horses that developed post-transfusion hepatitis. Plasma and serum from these horses were used to experimentally transmit EHCV to 4 young adult Arabian horses, two 1-month-old foals (1 Arabian and 1 Arabian-pony cross), and 2 foals (1 Arabian and 1 Arabian-pony cross) with severe combined immunodeficiency (SCID). Our results demonstrated that EHCV had infection kinetics similar to HCV and that infection was associated with acute and chronic liver disease as measured by elevations of liver-specific enzymes and/or by histopathology. Although most of these animals were coinfected with equine pegivirus (EPgV), also a flavivirus, EPgV viral loads were much lower and often undetectable in both liver and blood. Three additional young adult Arabian-pony crosses and 1 SCID foal were then inoculated with plasma containing only EHCV, and evidence of mild hepatocellular damage was observed. The different levels of liver-specific enzyme elevation, hepatic inflammation, and duration of viremia observed during EHCV infection suggested that the magnitude and course of liver disease was mediated by the virus inoculum and/or by host factors, including breed, age, and adaptive immune status. Conclusion: This work documents the complete infection kinetics and liver pathology associated with acute and chronic EHCV infection in horses and further justifies it as a large animal model for HCV. (Hepatology 2015;61:1533-1546)