A golden hamster model for human acute Nipah virus infection
A golden hamster model for human acute Nipah virus infection
复制标题
DOI：
10.1016/s0002-9440(10)63569-9
复制
发表时间：
2003-11-01
影响因子：
6
通讯作者：
Deubel, V
中科院分区：
文献类型：
--
作者：
Wong, KT;Grosjean, I;Deubel, V
最近出现了由新型尼帕病毒引起的主要由猪传染给人类的人畜共患感染，导致动物和人类严重发病和死亡。人体尸检研究表明，发病机制与系统性血管炎有关，系统性血管炎导致大多数主要器官尤其是中枢神经系统广泛的血栓闭塞和微梗死。还有血管外实质感染的证据，特别是在受损血管附近（Wong KT、Shleh VU、Kumar S、Norain K、Abdullah W、Guarner J、Goldsmith CS、Chua KB、Lam SK、Tan CT、Gob KJ、Chong HT、Jusoh R、Rollin PE、Ksiazek TG、Zaki SR、尼帕病毒病理学工作组：尼帕病毒感染：病理学和发病机制一种新出现的副粘病毒人畜共患病。Am J Pathol 2002, 161:21532167）。我们在这里描述了一个金仓鼠（Mesocricetus auratus）模型，它似乎重现了人类急性尼帕病毒感染的病理学和发病机制。通过鼻内或腹膜内途径感染的仓鼠分别在9至29天内或5至9天内死亡。仓鼠大脑的病理损伤最为严重和广泛。在多个器官的血管中发现了血管炎、血栓形成，以及更罕见的多核内皮合胞体。免疫组织化学和原位杂交分别证明，病毒抗原和 RNA 定位于血管和血管外组织，包括神经元、肺、肾和脾。在神经元和血管壁中鉴定出副粘病毒型核衣壳。在感染的末期，可以从大多数固体器官和尿液中回收病毒和/或病毒RNA，但不能从血清中回收。金仓鼠被提议作为进一步研究的合适模型，包括发病机制研究、抗病毒药物测试和针对急性尼帕感染的疫苗开发。
A predominantly pig-to-human zoonotic infection caused by the novel Nipah virus emerged recently to cause severe morbidity and mortality in both animals and man. Human autopsy studies showed the pathogenesis to be related to systemic vasculitis that led to widespread thrombotic occlusion and microinfarction in most major organs especially in the central nervous system. There was also evidence of extravascular parenchymal infection, particularly near damaged vessels (Wong KT, Shleh VU, Kumar S, Norain K, Abdullah W, Guarner J, Goldsmith CS, Chua KB, Lam SK, Tan CT, Gob KJ, Chong HT, Jusoh R, Rollin PE, Ksiazek TG, Zaki SR, Nipah Virus Pathology Working Group: Nipah virus infection: Pathology and pathogenesis of an emerging paramyxoviral zoonosis. Am J Pathol 2002, 161:21532167). we describe here a golden hamster (Mesocricetus auratus) model that appears to reproduce the pathology and pathogenesis of acute human Nipah infection. Hamsters infected by intranasal or intraperitoneal routes died within 9 to 29 days or 5 to 9 days, respectively. Pathological lesions were most severe and extensive in the hamster brain. Vasculitis, thrombosis, and more rarely, multinucleated endothelial syncytia, were found in blood vessels of multiple organs. Viral antigen and RNA were localized in both vascular and extravascular tissues including neurons, lung, kidney, and spleen, as demonstrated by immunohistochemistry and in situ hybridization, respectively. Paramyxoviral-type nudeocapsids were identified in neurons and in vessel walls. At the terminal stage of infection, virus and/or viral RNA could be recovered from most solid organs and urine, but not from serum. The golden hamster is proposed as a suitable model for further studies including pathogenesis studies, anti-viral drug testing, and vaccine development against acute Nipah infection.