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.

寨卡病毒(ZIKV)是一种由蚊子传播的黄病毒，据报道目前正在26个国家和地区传播。 拉丁美洲和加勒比地区。虽然感染者通常没有症状或只有轻微的 症状，新的证据开始将ZIKV感染与胎儿和新生儿小头畸形和严重的 神经系统并发症，如格林-巴利综合征。世界卫生组织宣布中国进入公共卫生紧急状态 2016年2月1日国际关注。虽然ZIKV的结构、嗜性和致病机理在很大程度上 未知的是，最近的几项研究开始揭示该病毒的病原学。事实上，最近的研究 明和他的同事发表的文章证明了ZIKV特异性地感染人类神经前体细胞。 下一步重要的工作是阐明ZIKV与宿主相互作用的分子机制。一切都很好 据记载，一旦病毒进入宿主细胞，它就会劫持细胞机器，主要是通过直接的、物理的 与宿主蛋白质接触。因此，构建ZIKV-宿主蛋白-蛋白质相互作用网络将具有重要意义 有助于我们理解ZIKV生命周期的分子机制。此外，ZIKV的比较- 宿主与登革病毒(DENV)的相互作用将为我们提供重要线索来识别新的 治疗靶点。具体来说，我们计划：1)构建ZIKV和DENV-宿主蛋白-蛋白质相互作用 网络；2)预测哪些宿主因素(S)在ZIKV-宿主相互作用中起重要作用；3)新验证 使用基于细胞的方法确定ZIKV宿主PPI。这个项目的成功将为我们提供一个全球性的PPI ZIKV与人类蛋白质组之间的网络。ZIKV-HOST和DENV-HOST PPI网络的比较 将提高我们识别重要的宿主因子和/或通常被利用的途径的可能性 被黄病毒感染。我们相信，PPI数据集将成为识别小说的重要踏脚石 药物靶点将极大地促进新疗法和疫苗的开发。