Viral Special Pathogens Branch, Division of High Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Viral Special Pathogens Branch, Division of High Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Antiviral Res. 2020 Feb;174:104702. doi: 10.1016/j.antiviral.2019.104702. Epub 2020 Jan 22.
For more than 20 years, researchers have used laboratory mice lacking type I or both type I and II interferon (IFN) responses to study high-containment viruses that cause hemorrhagic fevers (HF) in humans. With the exception of Rift Valley fever virus, agents that cause viral HF in humans, such as Ebola and Lassa virus, do not cause disease in mature immunocompetent mice. In contrast, IFN-deficient mice typically develop severe or fatal disease when inoculated with these agents. The sensitivity of IFN-deficient mice to disease has led to their widespread use in biocontainment laboratories to assess the efficacy of novel vaccines against HF viruses, often without considering whether adaptive immune responses in IFN-deficient mice accurately mirror those in immunocompetent humans. Failure to recognize these questions may lead to inappropriate expectations of the predictive value of mouse experiments. In two invited articles, we investigate these questions. The present article reviews the use of IFN-deficient mice for assessing novel vaccines against HF viruses, including Ebola, Lassa, Crimean-Congo hemorrhagic fever and Rift Valley fever viruses. A companion paper examines the general question of how the lack of IFN signaling may affect adaptive immune responses and the outcome of vaccine studies in mice.
20 多年来，研究人员一直使用缺乏 I 型或 I 型和 II 型干扰素（IFN）反应的实验室小鼠来研究引起人类出血热（HF）的高传染性病毒。除裂谷热病毒外，引起人类病毒性 HF 的病原体，如埃博拉病毒和拉萨热病毒，不会使成熟的免疫功能正常的小鼠发病。相比之下，用这些制剂接种 IFN 缺陷型小鼠通常会导致严重或致命疾病。IFN 缺陷型小鼠对疾病的敏感性导致它们在生物隔离实验室中被广泛用于评估针对 HF 病毒的新型疫苗的功效，通常没有考虑到 IFN 缺陷型小鼠中的适应性免疫反应是否准确反映了免疫功能正常的人类的反应。未能认识到这些问题可能导致对小鼠实验预测价值的不适当期望。在两篇特邀文章中，我们探讨了这些问题。本文综述了 IFN 缺陷型小鼠在评估针对 HF 病毒（包括埃博拉病毒、拉萨热病毒、克里米亚-刚果出血热病毒和裂谷热病毒）的新型疫苗中的应用。一篇配套论文探讨了缺乏 IFN 信号传导如何影响适应性免疫反应以及 IFN 信号传导缺失对小鼠疫苗研究结果的一般问题。
