Enabled interferon signaling evasion in an immune-competent transgenic mouse model of parainfluenza virus 5 infection
Enabled interferon signaling evasion in an immune-competent transgenic mouse model of parainfluenza virus 5 infection
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DOI：
10.1016/j.virol.2007.10.001
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发表时间：
2008-02-05
期刊：
影响因子：
3.7
通讯作者：
Horvath, Curt M.
中科院分区：
文献类型：
--
作者：
Kraus, Thomas A.;Garza, Lily;Horvath, Curt M.
副流感病毒5 （PIV5或SV5）感染几种哺乳动物物种，但在小鼠体内的有效复制受到限制。在人类中，PIV5通过靶向STAT1，在stat2依赖性反应中降解蛋白酶体，从而避开IFN信号。相反，细胞培养实验表明，分化的小鼠STAT2蛋白不能支持STAT1靶向。人STAT2在小鼠细胞中的表达可以克服物种限制，使piv5诱导的STAT1降解和随后的IFN拮抗成为可能。在这里，我们描述了一种无处不在表达人类STAT2的转基因小鼠。PIV5感染诱导STAT1降解，导致转基因小鼠细胞中的病毒复制和蛋白表达增强，而非转基因小鼠细胞中的病毒复制和蛋白表达增强。重要的是，与野生型幼鼠相比，鼻内接种PIV5导致转基因小鼠肺部病毒载量增加。这些转基因小鼠为研究先天免疫逃避在副粘病毒发病机制中的作用提供了小动物模型。(c) 2007爱思唯尔公司版权所有。
Parainfluenza virus 5 (PIV5 or SV5) infects several mammalian species but is restricted from efficient replication in mice. In humans, PIV5 evades IFN signaling by targeting STAT1 for proteasomal degradation in a STAT2-dependent reaction. In contrast, cell culture experiments have demonstrated that the divergent murine STAT2 protein fails to support STAT1 targeting. Expression of human STAT2 in mouse cells can overcome the species restriction to enable PIV5-induced STAT1 degradation and subsequent IFN antagonism. Here, we describe a transgenic mouse that ubiquitously expresses human STAT2. PIV5 infection induces STAT1 degradation leading to enhanced virus replication and protein expression in the cells from the transgenic mouse but not from the non-transgenic littermates. Importantly, intranasal inoculation with PIV5 results in increased viral load in the lungs of the transgenic mice compared to wild-type littermates. These transgenic mice provide a small animal model to study the role of innate immune evasion in paramyxovirus pathogenesis. (c) 2007 Elsevier Inc. All rights reserved.