Coordinated regulation and widespread cellular expression of interferon-stimulated genes (ISG) ISG-49, ISG-54, and ISG-56 in the central nervous system after infection with distinct viruses
Coordinated regulation and widespread cellular expression of interferon-stimulated genes (ISG) ISG-49, ISG-54, and ISG-56 in the central nervous system after infection with distinct viruses
复制标题
DOI：
10.1128/jvi.01167-06
复制
发表时间：
2007-01-01
影响因子：
5.4
通讯作者：
Campbell, Iain L.
中科院分区：
文献类型：
--
作者：
Wacher, Christie;Muller, Marcus;Campbell, Iain L.
干扰素（IFN）刺激基因（ISG）ISG-49、ISG-54和ISG-56对病毒感染高度应答，但这些基因在体内的调控和功能尚不清楚。我们研究了在感染淋巴细胞性脉络丛脑膜炎病毒（LCMV）或西尼罗河病毒（WNV）的小鼠大脑中这些ISGs的同时调节。在LCMV感染期间，ISG-49和ISG-56基因的表达显著增加，广泛分布并主要局限于常见和不同的神经元群体。ISG-54基因的表达也有所增加，但水平较低，分布更受限制。尽管ISG-49、ISG-54和ISG-56基因在LCMV感染的STAT 1和STAT 2敲除（KO）小鼠的脑中表达增加，但这是钝化的、延迟的，并限于脉络丛、脑膜和内皮。在野生型和STAT KO小鼠中，在LCW感染期间，ISG-56蛋白与脑中相应的RNA转录物平行调节。在感染WNV后的野生型小鼠脑中观察到ISG-49、ISG-54和ISG-56 RNA水平和ISG-56蛋白水平的类似变化。因此，在LCMV和WNV感染期间，ISG-49、ISG-54和ISG-56基因在脑中协同上调;在LCMV的情况下，这种上调完全（神经元）或部分（非神经元）依赖于IFN信号分子STAT 1和STAT 2。这些发现表明，ISG-49、ISG-54和ISG-56基因在中枢神经系统中对不同病毒的宿主反应中起主导作用，特别是在神经元中，这些基因可能具有非冗余功能。
The interferon (IFN)-stimulated genes (ISGs) ISG-49, ISG-54, and ISG-56 are highly responsive to viral infection, yet the regulation and function of these genes in vivo are unknown. We examined the simultaneous regulation of these ISGs in the brains of mice during infection with either lymphocytic choriomeningitis virus (LCMV) or West Nile virus (WNV). Expression of the ISG-49 and ISG-56 genes increased significantly during LCMV infection, being widespread and localized predominantly to common as well as distinct neuronal populations. Expression of the ISG-54 gene also increased but to lower levels and with a more restricted distribution. Although expression of the ISG-49, ISG-54, and ISG-56 genes was increased in the brains of LCMV-infected STAT1 and STAT2 knockout (KO) mice, this was blunted, delayed, and restricted to the choroid plexus, meninges, and endothelium. ISG-56 protein was regulated in parallel with the corresponding RNA transcript in the brain during LCW infection in wild-type and STAT KO mice. Similar changes in ISG-49, ISG-54, and ISG-56 RNA levels and ISG-56 protein levels were observed in the brains of wild-type mice following infection with WNV. Thus, the ISG-49, ISG-54, and ISG-56 genes are coordinately upregulated in the brain during LCMV and WNV infection; this upregulation, in the case of LCMV, was totally (neurons) or partially (non-neurons) dependent on the IFN-signaling molecules STAT1 and STAT2. These findings suggest a dominant role for the ISG-49, ISG-54, and ISG-56 genes in the host response to different viruses in the central nervous system, where, particularly in neurons, these genes may have nonredundant functions.