Construction of a ZIKV-host protein-protein interaction network

ZIKV-宿主蛋白-蛋白相互作用网络的构建

• 批准号: 9338992
• 负责人: Heng Zhu
• 金额: $ 24.53万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-16 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9338992
• 关键词: African; Algorithms; Bioinformatics; Biological Assay; Cambodian; Caribbean region; Cell Death; Cells; Co-Immunoprecipitations; Country; Coupled; Culicidae; Data; Data Set; Dengue Virus; Development; Embryo; Etiology; Event; Family; Flavivirus; Glycoproteins; Guillain-Barré Syndrome; Homologous Gene; Human; Immunoblot Analysis; Immunoprecipitation; Individual; Infection; Integration Host Factors; International; Japanese encephalitis virus; Label; Latin America; Lentivirus Infections; Life Cycle Stages; Link; Macaca mulatta; Microcephaly; Mission; Mitotic Cell Cycle; Molecular; Monkeys; Mus; National Institute of Allergy and Infectious Disease; Neurologic; Newborn Infant; Open Reading Frames; Pathogenesis; Pathway interactions; Play; Process; Proteins; Proteome; Public Health; Publishing; RNA Viruses; Reagent; Reporting; Resolution; Role; Sentinel; Serial Passage; Series; Structure; Symptoms; Testing; Ticks; Time; Tropism; Uganda; Validation; Viral Proteins; Virus; Virus Diseases; West Nile virus; Yellow fever virus; Zika Virus; base; cyanine dye 5; fetal; forest; improved; in vivo; induced pluripotent stem cell; nerve stem cell; new therapeutic target; novel therapeutics; novel vaccines; pathogen; progenitor; protein protein interaction; public health emergency; success; therapeutic target; transcriptome sequencing; virus host interaction; yeast protein

Zika virus (ZIKV), a mosquito-borne flavivirus, is now reported to be circulating in 26 countries and territories in Latin America and the Caribbean. While infected individuals can often be asymptomatic or have only mild symptoms, emerging evidence starts to link ZIKV infection to fetal and newborn microcephaly and serious neurological complications, such as Guillain-Barré syndrome. The WHO declared a Public Health Emergency of International Concern on Feb 1 of 2016. Though the structure, tropism and pathogenesis of ZIKV are largely unknown, several recent studies started to shed lights on the etiology of the virus. Indeed, recent studies published by Ming and colleagues demonstrated that ZIKV specifically infect human neuronal progenitor cells. The next important step is to elucidate the molecular mechanism of ZIKV-host interactions. It has been well documented that once a virus enters the host cell, it hijacks the cellular machineries, mainly via direct, physical contacts with host proteins. Therefore, construction of a ZIKV-host protein-protein interaction network will greatly facilitate our understanding of the molecular mechanism of ZIKV life cycle. In addition, comparison of the ZIKV- host interactions with dengue virus (DENV)-host interactions will provide us important clues to identify novel therapeutic targets. Specifically, we plan to: 1) Construct ZIKV and DENV-host protein-protein interaction networks; 2) Predict which host factor(s) plays an important role in ZIKV-host interactions; and 3) Validate newly identified ZIKV-host PPIs using cell-based approaches. The success of this project will provide us a global PPI network between ZIKV and human proteome. The comparison between ZIKV-host and DENV-host PPI networks will improve the likelihood for us to identify important host factors and/or pathways that are commonly exploited by the flavivirus. We believe that PPI datasets will serve as an important stepping stone towards identifying novel drug targets that will greatly facilitate development of novel therapeutics and vaccines.

据报道 拉丁美洲和加勒比海。虽然受感染的人通常无症状或只有中间 症状，新兴的证据开始将ZIKV感染与胎儿和新生儿小头畸形和严重 神经系统并发症，例如Guillain-Barré综合征。谁宣布公共卫生紧急 国际关注2016年2月1日。 未知，最近的几项研究开始对病毒的病因阐明。确实，最近的研究 Ming及其同事发表的表明，ZIKV专门感染了人类神经祖细胞。 下一个重要的步骤是阐明ZIKV-HOST相互作用的分子机制。很好 记录了一旦病毒进入宿主细胞，它将劫持蜂窝机器，主要是通过直接的物理 与宿主蛋白接触。因此，建造ZIKV-HOST蛋白 - 蛋白质相互作用网络将大大 促进我们对ZIKV生命周期分子机制的理解。此外，zikv-的比较 宿主与Fanguard病毒（DENV） - 宿主相互作用的相互作用将为我们提供重要的线索来识别新颖 治疗靶标。具体而言，我们计划：1）构建ZIKV和DENV-HOST蛋白 - 蛋白质相互作用 网络； 2）预测哪些宿主因子在ZIKV-host相互作用中起重要作用； 3）新近验证 使用基于细胞的方法鉴定了ZIKV-host PPI。该项目的成功将为我们提供全球PPI ZIKV和人类蛋白质组之间的网络。 ZIKV-host和DENV-主持PPI网络之间的比较 将改善我们确定通常被利用的重要宿主因素和/或途径的可能性 通过黄病毒。我们认为，PPI数据集将成为识别小说的重要垫脚石 将大大促进新疗法和疫苗开发的药物靶标。