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探索人-尼帕病毒蛋白质-蛋白质相互作用组

Exploring the Human-Nipah Virus Protein-Protein Interactome.

作者信息

Martinez-Gil Luis, Vera-Velasco Natalia M, Mingarro Ismael

机构信息

Department of Biochemistry and Molecular Biology, ERI BioTecMed, University of Valencia, Valencia, Spain

Department of Biochemistry and Molecular Biology, ERI BioTecMed, University of Valencia, Valencia, Spain.

出版信息

J Virol. 2017 Nov 14;91(23). doi: 10.1128/JVI.01461-17. Print 2017 Dec 1.

Abstract

Nipah virus is an emerging, highly pathogenic, zoonotic virus of the 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. 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.

摘要

尼帕病毒是该病毒家族中一种新出现的、高致病性的人畜共患病毒。人通过与受感染动物密切接触、食用受污染食物或偶尔通过其他受感染个体而发生传播。目前,我们缺乏针对尼帕病毒的治疗或预防方法。为了研发这些药物,我们现在必须加深对支持有效感染的宿主 - 病毒相互作用的理解。这一目标促使我们开展了本项研究,在此研究中我们鉴定出了101种人 - 尼帕病毒蛋白质 - 蛋白质相互作用(PPI),其中大部分(88种)是新发现的。该数据集全面展示了被病毒蛋白操纵的宿主复合物。宿主靶点包括PRP19复合物和微小RNA(miRNA)加工机制。此外,我们探究了与PRP19复合物相互作用的生物学后果,发现尼帕病毒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开发新的干预策略以应对这种新出现的病毒威胁。尼帕病毒是一种最近发现的病毒,可感染包括人类在内的多种哺乳动物。自发现以来每年都有疫情爆发,在一些疫情中确诊病例的死亡率达到了100%。然而,对尼帕病毒的研究在很大程度上被忽视了,目前我们缺乏针对这种感染的治疗方法。为了研发这些药物,我们现在必须加深对支持有效感染的宿主 - 病毒相互作用的理解。在本项研究中,我们采用亲和纯化方法结合质谱鉴定出了101种人 - 尼帕病毒蛋白质 - 蛋白质相互作用。此外,我们探究了其中一些相互作用的细胞后果。总体而言,该数据集全面而详细地展示了宿主机制对尼帕病毒生命周期的贡献。此外,我们的数据呈现了大量可用于治疗这种感染的潜在药物靶点。

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