Comparative Analysis of Monkeypox Virus Infection of Cynomolgus Macaques by the Intravenous or Intrabronchial Inoculation Route
Comparative Analysis of Monkeypox Virus Infection of Cynomolgus Macaques by the Intravenous or Intrabronchial Inoculation Route
复制标题
DOI：
10.1128/jvi.01931-10
复制
发表时间：
2011-03-01
影响因子：
5.4
通讯作者：
Jahrling, Peter B.
中科院分区：
文献类型：
--
作者：
Johnson, Reed F.;Dyall, Julie;Jahrling, Peter B.
猴痘病毒 (MPXV) 感染的地理分布最近有所扩大，高达 10% 的病例可能致命。与人类自然发生的 MPXV 感染相比，非人灵长类动物 (NHP) 的静脉内 (i.v.) 接种会导致暴发性疾病进程加速。正在研究替代的接种途径，以定义更接近自然疾病进展的 NHP 感染模型。我们的目标是确定 NHP 支气管内 (i.b.) 暴露于 MPXV 是否会导致更类似于人类 MPXV 感染进展的全身性疾病。在这里，我们比较了静脉注射后的病程。或 i.b.用 10 倍系列剂量的 MPXV Zaire 接种 NHP。通过任一途径施用高剂量病毒的 NHP 中都观察到了经典的痘样疾病。在 i.b. 测试的最高剂量下，几个关键事件被延迟。模型与静脉注射时间的比较模型，包括发烧发作、病变外观、病毒血症峰值、鼻腔和口腔拭子中的病毒脱落、细胞因子峰值水平以及达到终点标准的时间。在最高测试剂量下，病毒在 19 个组织中的分布基本上不受接种途径的影响。由 i.b 接种的 NHP。路线发展为病毒性肺炎，可能加剧疾病进展。根据对临床和病毒学参数延迟发作的观察以及可能更接近人类 MPXV 感染的终点标准，i.b.进一步研究病毒发病机制和对策应考虑MPXV模型。
Monkeypox virus (MPXV) infection has recently expanded in geographic distribution and can be fatal in up to 10% of cases. The intravenous (i.v.) inoculation of nonhuman primates (NHPs) results in an accelerated fulminant disease course compared to that of naturally occurring MPXV infection in humans. Alternative routes of inoculation are being investigated to define an NHP model of infection that more closely resembles natural disease progression. Our goal was to determine if the intrabronchial (i.b.) exposure of NHPs to MPXV results in a systemic disease that better resembles the progression of human MPXV infection. Here, we compared the disease course following an i.v. or i.b. inoculation of NHPs with 10-fold serial doses of MPXV Zaire. Classical pox-like disease was observed in NHPs administered a high virus dose by either route. Several key events were delayed in the highest doses tested of the i.b. model compared to the timing of the i.v. model, including the onset of fever, lesion appearance, peak viremia, viral shedding in nasal and oral swabs, peak cytokine levels, and time to reach endpoint criteria. Virus distribution across 19 tissues was largely unaffected by the inoculation route at the highest doses tested. The NHPs inoculated by the i.b. route developed a viral pneumonia that likely exacerbated disease progression. Based on the observations of the delayed onset of clinical and virological parameters and endpoint criteria that may more closely resemble those of human MPXV infection, the i.b. MPXV model should be considered for the further investigation of viral pathogenesis and countermeasures.