PACT, a double-stranded RNA binding protein acts as a positive regulator for type 1 interferon gene induced by Newcastle disease virus
PACT, a double-stranded RNA binding protein acts as a positive regulator for type 1 interferon gene induced by Newcastle disease virus
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DOI：
10.1006/bbrc.2001.4606
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发表时间：
2001-03-30
影响因子：
3.1
通讯作者：
Fujita, T
中科院分区：
文献类型：
--
作者：
Iwamura, T;Yoneyama, M;Fujita, T
病毒感染会触发对宿主细胞的先天反应，包括产生I型干扰素（IFN）。由于还通过使用聚（I：C）处理IFN产生，因此已经假定病毒双链（DS）RNA在该过程中起着直接作用。在本研究中，我们研究了DSRNA结合蛋白对病毒诱导的IFN-β基因激活的影响。我们发现，最初被确定为DSRNA依赖性蛋白激酶（PKR）的蛋白激活剂的PACT与翻译的调节有关，增强了由纽卡斯尔病毒引起的IFN-β基因激活。与IFN-β增强子的增强活性同时，观察到NF-KAPPAB和IRF-3和IRF-7的活性增加。对于观察到的效果，Pact的DSRNA结合活性至关重要。我们确定了与推定目标分子相互作用的条约残基以发挥其功能。此外，在感染细胞中与病毒复制复合复合物共定位。因此，PACT的观察到的作用是新颖的，Pact参与了病毒复制的调节，并导致细胞IFN-β基因表达显着增加。 （c）2001学术出版社。
Virus infection triggers innate responses to host cells including production of type I interferon (IFN). Since IFN production is also induced by treatment with poly(I:C), viral double-stranded (ds) RNA has been postulated to play a direct role in the process. In the present study, we investigated the effect of dsRNA binding proteins on virus-induced activation of the IFN-beta gene. We found that PACT, originally identified as protein activator for dsRNA-dependent protein kinase (PKR) and implicated in the regulation of translation, augmented IFN-beta gene activation induced by Newcastle disease virus. Concomitantly with the augmented activity of IFN-beta enhancer, increased activity of NF-kappaB and IRF-3 and IRF-7 was observed. For the observed effect, the dsRNA-binding activity of PACT was essential. We identified residues of PACT that interact with a presumptive target molecule to exert its function. Furthermore, PACT colocalized with viral replication complex in the infected cells. Thus the observed effect of PACT is novel and PACT is involved in the regulation of viral replication and results in a marked increase of cellular IFN-beta gene expression. (C) 2001 Academic Press.