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

基本信息

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
项目类别：
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

项目摘要

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，据报道目前在 26 个国家和地区传播。拉丁美洲和加勒比地区的感染者通常没有症状或只有轻微症状。随着症状的出现，新出现的证据开始将寨卡病毒感染与胎儿和新生儿小头畸形以及严重的畸形联系起来。神经系统并发症，例如吉兰-巴利综合征，世界卫生组织宣布该国进入公共卫生紧急状态。 2016年2月1日国际关注。认为ZIKV的结构、趋向性和发病机制很大程度上取决于未知，最近的几项研究开始揭示该病毒的病因。 Ming 及其同事发表的文章称，ZIKV 特异性感染人类神经元祖细胞。下一个重要步骤是阐明 ZIKV 与宿主相互作用的分子机制。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、物理的方式因此，ZIKV-宿主蛋白-蛋白相互作用网络的构建将极大地发挥作用。有助于我们了解ZIKV生命周期的分子机制。另外，ZIKV-的比较。宿主与登革热病毒（DENV）的相互作用将为我们提供识别新型病毒的重要线索具体来说，我们计划：1）构建 ZIKV 和 DENV 宿主蛋白间相互作用。网络；2) 预测哪些宿主因素在 ZIKV 与宿主的相互作用中发挥重要作用；3) 重新验证；使用基于细胞的方法识别了 ZIKV 宿主 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 宿主和 DENV 宿主 PPI 网络之间的比较。将提高我们识别重要宿主因子和/或常用途径的可能性我们相信 PPI 数据集将成为识别新型病毒的重要垫脚石。药物靶标将极大地促进治疗性小说和疫苗的开发。