Interferon α/β Receptor-Deficient Mice as a Model for Ebola Virus Disease
Interferon α/β Receptor-Deficient Mice as a Model for Ebola Virus Disease
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DOI：
10.1093/infdis/jiv215
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发表时间：
2015-10-01
影响因子：
6.4
通讯作者：
Dye, John M.
中科院分区：
文献类型：
--
作者：
Brannan, Jennifer M.;Froude, Jeffery W.;Dye, John M.
埃博拉病毒研究的一个主要障碍是缺乏苏丹病毒（SUDV）以及其他野生型（WT）埃博拉病毒的小动物模型。在这里，我们扩展了Bray和Lever等人的研究，这些研究表明WT埃博拉病毒在1型干扰素（IFN）α/β受体（IFN α/β R-/-）缺陷的小鼠中具有致病性。我们检查了几种WT埃博拉病毒的病程：Boneface（SUDV/Bon）和SUDV的Gulu变体、埃博拉病毒（EBOV）、本迪布焦病毒（BDBV）、Tai Forest病毒和Reston病毒（RESTV）。我们确定了暴露于WT SUDV或EBOV导致IFN α/β R-/-小鼠中可再现的疾病体征，如通过体重减轻和部分致死率所测量的。用表达SUDV或EBOV糖蛋白（GP）的委内瑞拉马脑炎病毒复制子颗粒疫苗接种分别保护这些小鼠免受SUDV/Bon和EBOV攻击。当在感染后1-3天递送时，用SUDV或EBOV特异性抗GP抗体治疗保护小鼠免受攻击。连续采样实验揭示了感染SUDV、EBOV和BDBV的Boneface变体的小鼠肝脏中弥散性血管内凝血的证据。总之，这些数据巩固了IFN α/β R-/-小鼠作为研究WT EBOV疾病的重要和有用的模型。
A major obstacle in ebolavirus research is the lack of a small-animal model for Sudan virus (SUDV), as well as other wild-type (WT) ebolaviruses. Here, we expand on research by Bray and by Lever et al suggesting that WT ebolaviruses are pathogenic in mice deficient for the type 1 interferon (IFN) alpha/beta receptor (IFN alpha/beta R-/-). We examined the disease course of several WT ebolaviruses: Boneface (SUDV/Bon) and Gulu variants of SUDV, Ebola virus (EBOV), Bundibugyo virus (BDBV), Tai Forest virus, and Reston virus (RESTV). We determined that exposure to WT SUDV or EBOV results in reproducible signs of disease in IFN alpha/beta R-/- mice, as measured by weight loss and partial lethality. Vaccination with the SUDV or EBOV glycoprotein (GP)-expressing Venezuelan equine encephalitis viral replicon particle vaccine protected these mice from SUDV/Bon and EBOV challenge, respectively. Treatment with SUDV-or EBOV-specific anti-GP antibodies protected mice from challenge when delivered 1-3 days after infection. Serial sampling experiments revealed evidence of disseminated intravascular coagulation in the livers of mice infected with the Boneface variant of SUDV, EBOV, and BDBV. Taken together, these data solidify the IFN alpha/beta R-/- mouse as an important and useful model for the study of WT EBOV disease.