Development of an Acute and Highly Pathogenic Nonhuman Primate Model of Nipah Virus Infection
Development of an Acute and Highly Pathogenic Nonhuman Primate Model of Nipah Virus Infection
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DOI：
10.1371/journal.pone.0010690
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发表时间：
2010-05-18
期刊：
影响因子：
3.7
通讯作者：
Broder, Christopher C.
中科院分区：
文献类型：
--
作者：
Geisbert, Thomas W.;Daddario-DiCaprio, Kathleen M.;Broder, Christopher C.
尼帕病毒（NiV）是一种神秘的新兴病原体，可在动物和人类中引起严重且通常致命的神经系统和/或呼吸系统疾病。在人群中，病死率在40%至75%之间，并且没有批准用于人类的疫苗或治疗方法。豚鼠、仓鼠、猫、雪貂、猪和最近的松鼠猴（新世界猴）已被评价为人类NiV感染的动物模型，除雪貂外，没有模型概括了人类中观察到的NiV介导的疾病的所有方面。为了确定一个更可行的非人灵长类动物（NHP）模型，我们研究了NiV在非洲绿色猴（AGM）的发病机制。将8只猴子暴露于NiV在所有8只动物中产生了严重的全身感染，其中7只动物死于感染。病毒RNA在激发动物的血浆中被检测到，并且在三名受试者中的两名受试者中在第7天和第21天之间出现峰值，首次明确证明了NiV实验感染动物中的血浆相关病毒血症，并表明从病毒复制的初始位点同时接种多个器官的进行性感染。与NiV感染的猫、仓鼠和松鼠猴模型不同，严重的呼吸道病理学、神经系统疾病和全身性血管炎都表现在NiV感染的AGM中，这准确反映了在NiV感染的人类中观察到的情况。我们的研究结果证明了NiV感染的第一个一致和高致病性NHP模型，为评估和许可人类使用的被动和主动免疫或治疗策略提供了一个新的关键平台。
Nipah virus (NiV) is an enigmatic emerging pathogen that causes severe and often fatal neurologic and/or respiratory disease in both animals and humans. Amongst people, case fatality rates range between 40 and 75 percent and there are no vaccines or treatments approved for human use. Guinea pigs, hamsters, cats, ferrets, pigs and most recently squirrel monkeys (New World monkey) have been evaluated as animal models of human NiV infection, and with the exception of the ferret, no model recapitulates all aspects of NiV-mediated disease seen in humans. To identify a more viable nonhuman primate (NHP) model, we examined the pathogenesis of NiV in African green monkeys (AGM). Exposure of eight monkeys to NiV produced a severe systemic infection in all eight animals with seven of the animals succumbing to infection. Viral RNA was detected in the plasma of challenged animals and occurred in two of three subjects as a peak between days 7 and 21, providing the first clear demonstration of plasma-associated viremia in NiV experimentally infected animals and suggested a progressive infection that seeded multiple organs simultaneously from the initial site of virus replication. Unlike the cat, hamster and squirrel monkey models of NiV infection, severe respiratory pathology, neurological disease and generalized vasculitis all manifested in NiV-infected AGMs, providing an accurate reflection of what is observed in NiV-infected humans. Our findings demonstrate the first consistent and highly pathogenic NHP model of NiV infection, providing a new and critical platform in the evaluation and licensure of either passive and active immunization or therapeutic strategies for human use.