Clinical Outcome of Henipavirus Infection in Hamsters Is Determined by the Route and Dose of Infection
Clinical Outcome of Henipavirus Infection in Hamsters Is Determined by the Route and Dose of Infection
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DOI：
10.1128/jvi.00473-11
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发表时间：
2011-08-01
影响因子：
5.4
通讯作者：
Feldmann, Heinz
中科院分区：
文献类型：
--
作者：
Rockx, Barry;Brining, Douglas;Feldmann, Heinz
尼帕病毒（NiV）和亨德拉病毒（HeV）是新出现的人畜共患病毒，也是人类严重呼吸道疾病和脑炎的病原体。人们对控制呼吸系统和神经系统疾病发展的机制知之甚少。利用致死性NiV和HeV的仓鼠模型，我们描述了感染途径和剂量对临床结果的作用，并确定了感染后病毒的趋向性和宿主反应。感染大剂量NiV或HeV的仓鼠可导致急性呼吸窘迫。NiV最初在上呼吸道上皮中复制，而HeV主要在间质中引起感染。相反，低剂量的NiV或HeV感染会导致神经系统症状的发展，并通过内皮细胞的参与使病毒更全面地传播。神经学症状的发展与血脑屏障（BBB）的破坏和肿瘤坏死α (tnf - α)和白细胞介素1 β (IL-1 β)的表达一致。此外，干扰素诱导蛋白10 （IP-10）在NiV和HeV发病机制中发挥重要作用。这些研究揭示了NiV和HeV临床疾病发生和进展的新信息，提供了NiV和HeV爆发之间传播差异的机制，并确定了作为重要治疗靶点的特定细胞因子和趋化因子。
Nipah virus (NiV) and Hendra virus (HeV) are emerging zoonotic viruses and the causative agents of severe respiratory disease and encephalitis in humans. Little is known about the mechanisms that govern the development of respiratory and neurological disease. Using a hamster model of lethal NiV and HeV infection, we describe the role of the route and dose of infection on the clinical outcome and determine virus tropism and host responses following infection. Infection of hamster with a high dose of NiV or HeV resulted in acute respiratory distress. NiV initially replicated in the upper respiratory tract epithelium, whereas HeV initiated infection primarily in the interstitium. In contrast, infection with a low dose of NiV or HeV resulted in the development of neurological signs and more systemic spread of the virus through involvement of the endothelium. The development of neurological signs coincided with disruption of the blood-brain barrier (BBB) and expression of tumor necrosis alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta). In addition, interferon-inducible protein 10 (IP-10) was identified as playing an important role in NiV and HeV pathogenesis. These studies reveal novel information on the development and progression of NiV and HeV clinical disease, provide a mechanism for the differences in transmission observed between NiV and HeV outbreaks, and identify specific cytokines and chemokines that serve as important targets for treatment.