Role of RNA helicase DDX1 in influenza A virus replication

项目总结： 流感病毒是一个世界性的公共卫生问题，有可能导致大流行。 虽然疫苗可以有效地保护个人免受流感病毒的感染，但仍有 非常需要能够防止疾病发展和病毒传播的抗病毒药物。因此， 需要努力研究流感病毒与宿主的相互作用，这对开发 抗流感病毒的新药，包括广谱药物。像其他病毒一样， 流感病毒依赖宿主细胞成分来完成病毒生命的大部分步骤 周而复始。这个项目的长期目标是确定控制 甲型流感病毒的复制，使这些信息可以用于开发新的 抗病毒药物。流感病毒的ns1蛋白是一种主要的毒力因子，有助于 流感病毒复制通过对抗宿主抗病毒反应和调节 病毒复制的过程。NS1蛋白在很大程度上发挥着这些生理功能 通过与宿主细胞分子相互作用。通过定量蛋白质组学方法，它 最近发现甲型流感病毒的NS1蛋白与DEAD-BOX蛋白1相互作用 (DDX1)，一个可能含有死盒结构的RNA解旋酶。进一步的初步研究 证明DDX1的敲除显著减少了甲型流感病毒的复制 人肺上皮细胞，提示DDX1蛋白被甲型流感病毒和 起复制辅因子的作用。随之而来的是，DDX1的敲除导致显著 甲型流感病毒感染细胞中干扰素βmRNA水平下降，表明它发挥了作用 在调节I型干扰素的转录中起着重要作用。两个具体目标将是 在这个项目中被追查。目的1.研究DDX1促进甲型流感的机制 病毒复制。目的2.研究DDX调节β干扰素的机制 在甲型流感病毒感染细胞中的表达。研究结果将有助于理解 DDX1在甲型流感病毒复制中的作用及加深对流感病毒的认识- 主持人互动。这一结果可能会为设计新的流感控制策略提供参考 病毒感染。

PROJECT SUMMARY: Influenza virus is a worldwide public health problem and has the potential to cause a pandemic. While vaccines can efficiently protect individuals from infection with influenza virus, there is still a great need for antiviral drugs that prevent disease progression and virus transmission. Thus, efforts are needed to study the influenza virus-host interactions, which are critical for developing novel drugs against the influenza virus, including broad-spectrum drugs. Like other viruses, influenza viruses depend on host cellular components to complete most steps of the viral life cycle. The long-term goal of this project is to identify the critical host cellular proteins that control influenza A virus replication, so that the information can be used for the development of new antiviral drugs. The NS1 protein of influenza virus is a major virulence factor that facilitates influenza virus replication through countering host antiviral response and regulating various processes in virus replication. The NS1 protein exerts these physiological functions largely through interacting with host cellular molecules. Through a quantitative proteomic method, it was recently found that the NS1 protein of influenza A virus interacts with DEAD-box protein 1 (DDX1), a putative DEAD-box-containing RNA helicase. Further preliminary studies demonstrate that knockdown of DDX1 dramatically reduces influenza A virus replication in human lung epithelial cells, suggesting that DDX1 protein is “hijacked” by influenza A virus and functions as a replication cofactor. Concomitantly, knockdown of DDX1 leads to significant decreases in interferon beta mRNA levels in influenza A virus infected cells, suggesting it plays an important role in regulating the transcription of type I interferons. Two specific aims will be pursued in this project. Aim 1. Examine the mechanism by which DDX1 facilitates influenza A virus replication. Aim 2. Examine the mechanisms by which DDX regulates interferon beta expression in influenza A virus-infected cells. The results will contribute to understanding the role of DDX1 in influenza A virus replication and enhance the understanding of influenza virus- host interactions. The results may shed light on designing novel strategies to control influenza viral infection.