Development of mouse models for analysis of human virus infections
Development of mouse models for analysis of human virus infections
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开发用于分析人类病毒感染的小鼠模型
DOI：
10.1111/1348-0421.12477
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发表时间：
2017
影响因子：
2.6
通讯作者：
Seya Tsukasa
中科院分区：
文献类型：
--
作者：
Takaki Hiromi;Oshiumi Hiroyuki;Shingai Masashi;Matsumoto Misako;Seya Tsukasa
病毒通常表现出严格的种属特异性，这是与宿主共同进化的结果。因此，在小鼠模型中，分析嗜人病毒感染存在很大障碍。小鼠模型不太可能忠实地再现人类对病毒或病毒化合物的免疫应答，并且难以在小鼠模型中评价抗病毒试剂的人类治疗功效。人类和小鼠基本上有不同的免疫系统，这使得很难将小鼠的结果外推到人类身上。此外，除免疫学原因外，引起人类疾病的病毒由于种嗜性，并不总是感染小鼠。确定嗜性的一种方法是在受影响的细胞上表达的病毒受体。表达人类受体基因的基因破坏小鼠和Tg小鼠的发展使我们能够分析小鼠中的几种病毒感染。事实上，当在补充受体的小鼠中人工感染时，小鼠对人类病毒易感。尽管小鼠细胞允许病毒复制的效率低于人类细胞，但用于分析人类病毒的模型已经在体内和体外建立，并解释了小鼠系统中的病毒发病机制。然而，在大多数系统中，核酸传感器和I型干扰素抑制病毒繁殖以阻断感染表现的出现。我们在此综述了近年来对典型人类病毒在小鼠感染模型中诱导的体内抗病毒反应的研究进展。
Viruses usually exhibit strict species‐specificity as a result of co‐evolution with the host. Thus, in mouse models, a great barrier exists for analysis of infections with human‐tropic viruses. Mouse models are unlikely to faithfully reproduce the human immune response to viruses or viral compounds and it is difficult to evaluate human therapeutic efficacy with antiviral reagents in mouse models. Humans and mice essentially have different immune systems, which makes it difficult to extrapolate mouse results to humans. In addition, apart from immunological reasons, viruses causing human diseases do not always infect mice because of species tropism. One way to determine tropism would be a virus receptor that is expressed on affected cells. The development of gene‐disrupted mice and Tg mice, which express human receptor genes, enables us to analyze several viral infections in mice. Mice are, indeed, susceptible to human viruses when artificially infected in receptor‐supplemented mice. Although the mouse cells less efficiently permit viral replication than do human cells, the models for analysis of human viruses have been establishedin vivoas well asin vitro, and explain viral pathogenesis in the mouse systems. In most systems, however, nucleic acid sensors and type I interferon suppress viral propagation to block the appearance of infectious manifestation. We herein review recent insight intoin vivoantiviral responses induced in mouse infection models for typical human viruses.