Department of Biology, Georgia State University, Atlanta, GA 30302, USA.
Virology. 2012 Apr 10;425(2):82-94. doi: 10.1016/j.virol.2012.01.006. Epub 2012 Feb 3.
Although infection of mouse embryofibroblasts (MEFs) with WNV Eg101 induced interferon (IFN) beta production and STAT1 and STAT2 phosphorylation, these transcription factors (TFs) were not detected in the nucleus or on the promoters of four IRF-3-independent interferon stimulated genes (ISGs): Oas1a and Irf7 (previously characterized as IFN/ISGF3-dependent), Oas1b and Irf1. These ISGs were upregulated in WNV Eg101-infected STAT1-/-, STAT2-/-, and IFN alpha/beta receptor-/- MEFs. Although either IRF-3 or IRF-7 could amplify/sustain Oas1a and Oas1b upregulation at later times after infection, these factors were not required for the initial gene activation. The lack of upregulation of these ISGs in WNV Eg101-infected IRF-3/9-/- MEFs suggested the involvement of IRF-9. Activation of Irf1 in infected MEFs did not depend on any of these IRFs. The data indicate that additional alternative activation mechanisms exist for subsets of ISGs when a virus infection has blocked ISG activation by the canonical IFN-mediated pathway.
虽然西尼罗河病毒 Eg101 感染小鼠胚胎成纤维细胞（MEFs）会诱导干扰素（IFN）β的产生以及 STAT1 和 STAT2 的磷酸化，但这些转录因子（TFs）并未在核内或四个干扰素刺激基因（ISGs）的启动子上检测到：Oas1a 和 Irf7（先前被认为是 IFN/ISGF3 依赖性的）、Oas1b 和 Irf1。这些 ISGs 在 WNV Eg101 感染的 STAT1-/-、STAT2-/-和 IFNα/β受体-/- MEFs 中上调。虽然 IRF-3 或 IRF-7 可以在感染后较晚时间扩增/维持 Oas1a 和 Oas1b 的上调，但这些因子对于初始基因激活并非必需。IRF-3/9-/- MEFs 中 WNV Eg101 感染后这些 ISGs 的上调缺失表明 IRF-9 的参与。在感染的 MEFs 中，Irf1 的激活不依赖于这些 IRFs 中的任何一个。这些数据表明，当病毒感染阻断了经典 IFN 介导的途径对 ISG 的激活时，ISGs 的子集存在额外的替代激活机制。
