Histopathological features and distribution of EV71 antigens and SCARB2 in human fatal cases and a mouse model of enterovirus 71 infection
Histopathological features and distribution of EV71 antigens and SCARB2 in human fatal cases and a mouse model of enterovirus 71 infection
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DOI：
10.1016/j.virusres.2014.05.006
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发表时间：
2014-08-30
期刊：
影响因子：
5
通讯作者：
Qin, Chuan
中科院分区：
文献类型：
--
作者：
Yu, Pin;Gao, Zifen;Qin, Chuan
肠病毒71 （EV71）是一种致手足口病的嗜神经病原体。虽然感染通常是自限性的，但少数感染EV71型病毒的患者会出现严重的神经系统并发症。据报道，在人类中，EV71利用清道夫受体B类成员2 （SCARB2）作为感染性细胞进入的受体。在这项研究中，我们确定了EV71相关疾病的病理特征，以及EV71抗原和SCARB2在人类死亡病例和小鼠模型中的分布。在组织病理学上，人类死亡病例表现出严重的中枢神经系统（CNS）改变，主要在脑干、脊髓和丘脑。这些患者进一步表现为肺水肿和坏死性肠炎。对人死亡病例的免疫组化分析表明，EV71抗原和SCARB2主要存在于中枢神经系统的神经元、小胶质细胞和炎症细胞以及肠上皮细胞中。而骨骼肌组织EV71抗原阴性。在EV71感染小鼠模型中，我们观察到大量坏死性肌炎，中枢神经系统不同程度的病毒性疾病和广泛的间质性肺炎。与人类的嗜神经性相比，EV71在小鼠中表现出强烈的肌向性。在小鼠脊髓和脑干中检测到EV71抗原。然而，在小鼠模型中，小鼠SCARB2与EV71抗原分布之间没有明显的相关性，这与先前的结果一致，即SCARB2在人类中作为EV71受体而不是小鼠。在小鼠模型中观察到的ev71诱导的病变与在人类样本中观察到的病理变化相似。这些结果增加了我们对EV71发病机制的理解，并将为进一步开发EV71感染小鼠模型提供信息。(C) 2014 Elsevier B.V.版权所有
Enterovirus 71 (EV71) is a neurotropic pathogen that causes hand, foot, and mouth disease. While infection is usually self-limiting, a minority of patients infected with EV71 develop severe neurological complications. In humans, EV71 has been reported to utilize the scavenger receptor class B, member 2 (SCARB2) as a receptor for infectious cellular entry. In this study, we define the pathological features of EV71-associated disease as well as the distribution of EV71 antigen and SCARB2 in human fatal cases and a mouse model. Histopathologically, human fatal cases showed severe central nervous system (CNS) changes, mainly in the brainstems, spinal cords, and thalamus. These patient further exhibited pulmonary edema and necrotic enteritis. Immunohistochemical analysis of human fatal cases demonstrated that EV71 antigen and SCARB2 were observed mainly in neurons, microglia cells and inflammatory cells in the CNS, and epithelial cells in the intestines. However, skeletal muscle tissue was negative for EV71 antigen. In a mouse model of EV71 infection, we observed massive necrotic myositis, different degrees of viral diseases in CNS, and extensive interstitial pneumonia. In mice, EV71 exhibits strong myotropism compared to the neurotropism seen in humans. EV71 antigen was detected in the spinal cord and brainstem of mice. However, there was no clear correlation between mouse SCARB2 and EV71 antigen distribution in the mouse model, consistent with previous results that SCARB2 functions as a receptor for EV71 in humans but not mice. The EV71-induced lesions seen in the mouse model resembled the pathological changes seen in human samples. These results increase our understanding of EV71 pathogenesis and will inform further work developing a mouse model for EV71 infection. (C) 2014 Elsevier B.V. All rights reserved.