Center for Animal Health Research, INIA-CISA, 28130 Valdeolmos, Madrid, Spain.
Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510, USA.
Viruses. 2019 Jan 8;11(1):35. doi: 10.3390/v11010035.
Arboviruses are arthropod-borne viruses that exhibit worldwide distribution and are a constant threat, not only for public health but also for wildlife, domestic animals, and even plants. To study disease pathogenesis and to develop efficient and safe therapies, the use of an appropriate animal model is a critical concern. Adult mice with gene knockouts of the interferon α/β (IFN-α/β) receptor (IFNAR(-/-)) have been described as a model of arbovirus infections. Studies with the natural hosts of these viruses are limited by financial and ethical issues, and in some cases, the need to have facilities with a biosafety level 3 with sufficient space to accommodate large animals. Moreover, the number of animals in the experiments must provide results with statistical significance. Recent advances in animal models in the last decade among other gaps in knowledge have contributed to the better understanding of arbovirus infections. A tremendous advantage of the IFNAR(-/-) mouse model is the availability of a wide variety of reagents that can be used to study many aspects of the immune response to the virus. Although extrapolation of findings in mice to natural hosts must be done with care due to differences in the biology between mouse and humans, experimental infections of IFNAR(-/-) mice with several studied arboviruses closely mimics hallmarks of these viruses in their natural host. Therefore, IFNAR(-/-) mice are a good model to facilitate studies on arbovirus transmission, pathogenesis, virulence, and the protective efficacy of new vaccines. In this review article, the most important arboviruses that have been studied using the IFNAR(-/-) mouse model will be reviewed.
虫媒病毒是具有世界分布性的节肢动物传播病毒,它们不仅对公共卫生,而且对野生动物、家畜甚至植物都构成持续的威胁。为了研究疾病发病机制并开发有效且安全的疗法,使用适当的动物模型是一个关键问题。已经描述了干扰素 α/β(IFN-α/β)受体(IFNAR(-/-))基因敲除的成年小鼠作为虫媒病毒感染的模型。由于财务和伦理问题,以及在某些情况下需要具有足够空间容纳大型动物的生物安全级别 3 的设施,对这些病毒的天然宿主进行研究受到限制。此外,实验中动物的数量必须提供具有统计学意义的结果。在过去十年中,动物模型方面的最新进展以及其他知识空白有助于更好地了解虫媒病毒感染。IFNAR(-/-)小鼠模型的一个巨大优势是可获得广泛的试剂,可用于研究对病毒免疫反应的许多方面。尽管由于小鼠和人类之间生物学差异的原因,必须谨慎地将在小鼠中发现的结果外推到天然宿主,但用几种已研究的虫媒病毒对 IFNAR(-/-) 小鼠进行实验感染,可很好地模拟这些病毒在其自然宿主中的特征。因此,IFNAR(-/-) 小鼠是促进虫媒病毒传播、发病机制、毒力和新型疫苗保护效力研究的良好模型。在这篇综述文章中,将回顾使用 IFNAR(-/-) 小鼠模型研究的最重要的虫媒病毒。