FUSE Binding Protein 1 Interacts with Untranslated Regions of Japanese Encephalitis Virus RNA and Negatively Regulates Viral Replication
FUSE Binding Protein 1 Interacts with Untranslated Regions of Japanese Encephalitis Virus RNA and Negatively Regulates Viral Replication
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DOI：
10.1128/jvi.01950-10
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发表时间：
2011-05-01
影响因子：
5.4
通讯作者：
Lin, Yi-Ling
中科院分区：
文献类型：
--
作者：
Chien, Hsu-Ling;Liao, Ching-Len;Lin, Yi-Ling
非翻译区（untranslated regions，UTR）位于乙型脑炎病毒（Japanese encephalitis virus，JEV）基因组的5'端和3'端，是一种正义RNA，参与病毒的翻译、RNA合成的起始和新生病毒粒子的包装。参与这些过程的细胞和病毒蛋白预期与UTR相互作用。在这项研究中，我们使用生物素化的RNA-蛋白下拉和液相色谱-质谱/质谱（LC-MS/MS）分析来鉴定远上游元件（FUSE）结合蛋白1（FBP 1）与JEV 5'和3' UTR结合。在具有改变的FBP 1表达的细胞中确定FBP 1对JEV感染的影响。JEV的复制通过敲低而增强，通过FBP 1的过表达而减少，表明FBP 1在JEV感染中的负作用。FBP 1是一种核蛋白，在JEV感染的早期重新分布到核周区域，并出现与JEV RNA部分共定位的胞质灶。通过使用JEV复制子报告基因测定，FBP 1似乎抑制由5'和3' UTR介导的JEV蛋白表达。因此，我们认为FBP 1与JEV UTR RNA结合，并通过抑制病毒蛋白表达作为宿主抗JEV防御分子发挥作用。
The untranslated regions (UTRs) located at the 5' and 3' ends of the Japanese encephalitis virus (JEV) genome, a positive-sense RNA, are involved in viral translation, the initiation of RNA synthesis, and the packaging of nascent virions. The cellular and viral proteins that participate in these processes are expected to interact with the UTRs. In this study, we used biotinylated RNA-protein pulldown and liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) analyses to identify that the far upstream element (FUSE) binding protein 1 (FBP1) binds with JEV 5' and 3' UTRs. The impact of FBP1 on JEV infection was determined in cells with altered FBP1 expression. JEV replication was enhanced by knockdown and reduced by the overexpression of FBP1, indicating a negative role for FBP1 in JEV infection. FBP1, a nuclear protein, was redistributed to the perinuclear region and appeared as cytoplasmic foci that partially colocalized with JEV RNA in the early stage of JEV infection. By using a JEV replicon reporter assay, FBP1 appeared to suppress JEV protein expression mediated by the 5' and 3' UTRs. Thus, we suggest that FBP1 binds with the JEV UTR RNA and functions as a host anti-JEV defense molecule by repressing viral protein expression.