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Exploring the Human-Nipah Virus Protein-Protein Interactome
Journal of Virology ( IF 5.4 ) Pub Date : 2017-12-01 , DOI: 10.1128/jvi.01461-17
Luis Martinez-Gil 1 , Natalia M. Vera-Velasco 1 , Ismael Mingarro 1
Affiliation  

Nipah virus is an emerging, highly pathogenic, zoonotic virus of the Paramyxoviridae family. Human transmission occurs by close contact with infected animals, the consumption of contaminated food, or, occasionally, via other infected individuals. Currently, we lack therapeutic or prophylactic treatments for Nipah virus. To develop these agents we must now improve our understanding of the host-virus interactions that underpin a productive infection. This aim led us to perform the present work, in which we identified 101 human-Nipah virus protein-protein interactions (PPIs), most of which (88) are novel. This data set provides a comprehensive view of the host complexes that are manipulated by viral proteins. Host targets include the PRP19 complex and the microRNA (miRNA) processing machinery. Furthermore, we explored the biologic consequences of the interaction with the PRP19 complex and found that the Nipah virus W protein is capable of altering p53 control and gene expression. We anticipate that these data will help in guiding the development of novel interventional strategies to counter this emerging viral threat.

IMPORTANCE Nipah virus is a recently discovered virus that infects a wide range of mammals, including humans. Since its discovery there have been yearly outbreaks, and in some of them the mortality rate has reached 100% of the confirmed cases. However, the study of Nipah virus has been largely neglected, and currently we lack treatments for this infection. To develop these agents we must now improve our understanding of the host-virus interactions that underpin a productive infection. In the present work, we identified 101 human-Nipah virus protein-protein interactions using an affinity purification approach coupled with mass spectrometry. Additionally, we explored the cellular consequences of some of these interactions. Globally, this data set offers a comprehensive and detailed view of the host machinery's contribution to the Nipah virus's life cycle. Furthermore, our data present a large number of putative drug targets that could be exploited for the treatment of this infection.



中文翻译:

探索人类尼帕病毒蛋白-蛋白质相互作用组

Nipah病毒是副粘病毒科的一种新兴的高致病性人畜共患病毒家庭。人类传播是通过与受感染的动物密切接触,食用受污染的食物或偶尔通过其他受感染的个体进行的。目前,我们缺乏尼帕病毒的治疗或预防方法。为了开发这些代理,我们现在必须增进对支持生产性感染的宿主-病毒相互作用的了解。此目标使我们执行了当前的工作,其中我们确定了101种人与尼帕病毒的蛋白质-蛋白质相互作用(PPI),其中大多数(88)是新颖的。该数据集提供了由病毒蛋白操纵的宿主复合物的全面视图。宿主靶标包括PRP19复合物和microRNA(miRNA)处理设备。此外,我们探索了与PRP19复合物相互作用的生物学后果,并发现Nipah病毒W蛋白能够改变p53调控和基因表达。我们预计这些数据将有助于指导新型干预策略的发展,以应对这种新兴的病毒威胁。

重要性Nipah病毒是最近发现的一种病毒,可感染包括人类在内的多种哺乳动物。自从发现以来,每年都有暴发,其中一些疾病的死亡率已达到确诊病例的100%。但是,对尼帕病毒的研究一直被忽略,目前我们还没有针对这种感染的治疗方法。为了开发这些代理,我们现在必须增进对支持生产性感染的宿主-病毒相互作用的了解。在目前的工作中,我们使用亲和纯化方法和质谱法鉴定了101种人-尼帕病毒的蛋白-蛋白相互作用。此外,我们探索了其中一些相互作用的细胞后果。在全球范围内,该数据集提供了宿主机械对Nipah病毒的贡献的全面详细视图。的生命周期。此外,我们的数据显示了可用于治疗这种感染的大量推定药物靶标。

更新日期:2017-11-15
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