A novel mechanism for the inhibition of interferon regulatory factor-3-dependent gene expression by human respiratory syncytial virus NS1 protein.
A novel mechanism for the inhibition of interferon regulatory factor-3-dependent gene expression by human respiratory syncytial virus NS1 protein.
复制标题
人呼吸道合胞病毒 NS1 蛋白抑制干扰素调节因子 3 依赖性基因表达的新机制。
DOI：
10.1099/vir.0.032987-0
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Bao,Xiaoyong
中科院分区：
文献类型：
--
作者：
Ren,Junping;Liu,Tianshuang;Pang,Lan;Li,Kui;Garofalo,RobertoP;Casola,Antonella;Bao,Xiaoyong
Human respiratory syncytial virus (RSV), a leading cause of respiratory tract infections in infants, inhibits type I interferon (IFN)-dependent signalling, as well as IFN synthesis. RSV non-structural protein NS1 plays a significant role in this inhibition; however, the mechanism(s) responsible is not fully known. The transcription factor interferon regulatory factor (IRF)-3 is essential for viral-induced IFN-β synthesis. In this study, we found that NS1 protein inhibits IRF-3-dependent gene transcription in constitutively active IRF-3 overexpressing cells, demonstrating that NS1 directly targets IRF-3. Our data also demonstrate that NS1 associates with IRF-3 and its transcriptional coactivator CBP, leading to disrupted association of IRF-3 to CBP and subsequent reduced binding of IRF-3 to the IFN-β promoter without blocking viral-induced IRF-3 phosphorylation, nuclear translocation and dimerization, thereby identifying a novel molecular mechanism by which RSV inhibits IFN-β synthesis.
