Brannan Jennifer M, Froude Jeffery W, Prugar Laura I, Bakken Russell R, Zak Samantha E, Daye Sharon P, Wilhelmsen Catherine E, Dye John M
US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland.
J Infect Dis. 2015 Oct 1;212 Suppl 2:S282-94. doi: 10.1093/infdis/jiv215. Epub 2015 May 4.
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) α/β receptor (IFNα/βR-/-). We examined the disease course of several WT ebolaviruses: Boneface (SUDV/Bon) and Gulu variants of SUDV, Ebola virus (EBOV), Bundibugyo virus (BDBV), Taï Forest virus, and Reston virus (RESTV). We determined that exposure to WT SUDV or EBOV results in reproducible signs of disease in IFNα/βR-/- 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 IFNα/βR-/- mouse as an important and useful model for the study of WT EBOV disease.
埃博拉病毒研究中的一个主要障碍是缺乏针对苏丹病毒（SUDV）以及其他野生型（WT）埃博拉病毒的小动物模型。在此，我们拓展了布雷（Bray）以及利弗（Lever）等人的研究，他们提出野生型埃博拉病毒对缺乏1型干扰素（IFN）α/β受体（IFNα/βR -/-）的小鼠具有致病性。我们研究了几种野生型埃博拉病毒的病程：博内法斯（SUDV/Bon）和苏丹病毒的古卢变种、埃博拉病毒（EBOV）、本迪布焦病毒（BDBV）、塔伊森林病毒以及雷斯顿病毒（RESTV）。我们确定，通过体重减轻和部分致死率来衡量，暴露于野生型苏丹病毒或埃博拉病毒会在IFNα/βR -/-小鼠中引发可重现的疾病迹象。用表达苏丹病毒或埃博拉病毒糖蛋白（GP）的委内瑞拉马脑炎病毒复制子颗粒疫苗进行接种，分别保护这些小鼠免受博内法斯型苏丹病毒和埃博拉病毒的攻击。在感染后1至3天给予苏丹病毒或埃博拉病毒特异性抗GP抗体进行治疗，可保护小鼠免受攻击。连续采样实验揭示了感染博内法斯型苏丹病毒、埃博拉病毒和本迪布焦病毒的小鼠肝脏中存在弥散性血管内凝血的证据。综上所述，这些数据巩固了IFNα/βR -/-小鼠作为研究野生型埃博拉病毒病的重要且有用模型的地位。
