Laboratory of Virology, Rocky Mountain Laboratories, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, United States.
Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, United States.
Front Cell Infect Microbiol. 2018 Apr 11;8:117. doi: 10.3389/fcimb.2018.00117. eCollection 2018.
The common small animal disease models for Zika virus (ZIKV) are mice lacking the interferon responses, but infection of interferon receptor α/β knock out (IFNAR) mice is not uniformly lethal particularly in older animals. Here we sought to advance this model in regard to lethality for future countermeasure efficacy testing against more recent ZIKV strains from the Asian lineage, preferably the American sublineage. We first infected IFNAR mice subcutaneously with the contemporary ZIKV-Paraiba strain resulting in predominantly neurological disease with ~50% lethality. Infection with ZIKV-Paraiba by different routes established a uniformly lethal model only in young mice (4-week old) upon intraperitoneal infection. However, intraperitoneal inoculation of ZIKV-French Polynesia resulted in uniform lethality in older IFNAR mice (10-12-weeks old). In conclusion, we have established uniformly lethal mouse disease models for efficacy testing of antivirals and vaccines against recent ZIKV strains representing the Asian lineage.
寨卡病毒（ZIKV）的常见小动物疾病模型是缺乏干扰素反应的小鼠，但干扰素受体 α/β 敲除（IFNAR）小鼠的感染并非普遍致命，尤其是在老年动物中。在这里，我们试图针对最近来自亚洲谱系的寨卡病毒的致死性，改进这种模型，最好是针对来自美国亚谱系的病毒。我们首先通过皮下途径用当代的寨卡病毒-帕拉伊巴株感染 IFNAR 小鼠，导致主要是神经疾病，死亡率约为 50%。通过不同途径感染寨卡病毒-帕拉伊巴株仅在腹腔感染的年轻小鼠（4 周龄）中建立了一种均匀致死的模型。然而，寨卡病毒-法属波利尼西亚株的腹腔接种在老年 IFNAR 小鼠（10-12 周龄）中导致了均匀的致死性。总之，我们已经建立了针对最近代表亚洲谱系的寨卡病毒株的抗病毒药物和疫苗的疗效测试的均匀致死性小鼠疾病模型。
