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，据报道目前在全球26个国家和地区传播