C and V proteins of Sendai virus target signaling pathways leading to IRF-3 activation for the negative regulation of interferon-β production
C and V proteins of Sendai virus target signaling pathways leading to IRF-3 activation for the negative regulation of interferon-β production
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DOI：
10.1016/j.virol.2004.04.025
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发表时间：
2004-07-20
期刊：
影响因子：
3.7
通讯作者：
Gotoh, B
中科院分区：
文献类型：
--
作者：
Komatsu, T;Takeuchi, K;Gotoh, B
我们在此报告了仙台病毒 (SeV) V 和 C 蛋白下调干扰素 (IFN)-β 产生的分子基础。即使 C/C' 的表达被破坏，SeV 感染 HeLa 细胞也很难诱导 IFN-β。相反，当C/C'/Y1/Y2或V/W的表达被破坏时，SeV感染强烈诱导IFN-β产生并显着激活干扰素调节因子(IRF)-3途径。 C或V的独立表达抑制双链(ds)RNA或新城疫病毒(NDV)诱导的IRF-3和NF-κB以及IFN-β启动子的激活。当Y1、Y2或C的C末端半片段(aa 85-204)独立表达时也观察到这种抑制效果。 IRF-3 的磷酸化和同型二聚体形成不仅在能够表达 C/C'/Y1/Y2（或 Y1/Y2）和 V/W 的 SeV 感染的细胞中受到抑制，而且在组成型表达 Y1 的 HeLa 细胞中也受到抑制。这些结果表明，C、Y1、Y2 和 V 阻断导致 IRF-3 激活的信号通路，从而下调 IFN-β 的产生。 (C) 2004 Elsevier Inc. 保留所有权利。
We here report a molecular basis for downregulation of interferon (IFN)-beta production by V and C proteins of Sendai virus (SeV). The infection of HeLa cells with SeV poorly induced IFN-beta even if the expression of C/C' was disrupted. In contrast, when the expression of C/C'/Y1/Y2 or V/W was disrupted, SeV infection strongly induced IFN-beta production and significantly activated the interferon regulatory factor (IRF)-3 pathway. The independent expression of C or V inhibited the double-stranded (ds) RNA- or Newcastle disease virus (NDV)-induced activation of IRF-3 and NF-kappaB, as well as the IFN-beta promoter. This inhibitory effect was also observed when Y1, Y2, or a C-terminal half fragment (aa 85-204) of C was independently expressed. Phosphorylation and homodimer formation of IRF-3 were suppressed not only in cells infected with SeV capable of expressing both C/C'/Y1/Y2 (or Y1/Y2) and V/W, but also in HeLa cells constitutively expressing Y1. These results suggest that C, Y1, Y2, and V block signaling pathways leading to IRF-3 activation to downregulate IFN-beta production. (C) 2004 Elsevier Inc. All rights reserved.