Construction of a ZIKV-host protein-protein interaction network
Construction of a ZIKV-host protein-protein interaction network
批准号:
9338992
负责人:
Heng Zhu
金额:
$24.53万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2017
资助国家:
美国
项目状态:
已结题
起止时间:
2017-08-16 至 2019-07-31
关键词:
AfricanAlgorithmsBioinformaticsBiological AssayCambodianCaribbean regionCell DeathCellsCo-ImmunoprecipitationsCountryCoupledCulicidaeDataData SetDengue VirusDevelopmentEmbryoEtiologyEventFamilyFlavivirusGlycoproteinsGuillain-Barré SyndromeHomologous GeneHumanImmunoblot AnalysisImmunoprecipitationIndividualInfectionIntegration Host FactorsInternationalJapanese encephalitis virusLabelLatin AmericaLentivirus InfectionsLife Cycle StagesLinkMacaca mulattaMicrocephalyMissionMitotic Cell CycleMolecularMonkeysMusNational Institute of Allergy and Infectious DiseaseNeurologicNewborn InfantOpen Reading FramesPathogenesisPathway interactionsPlayProcessProteinsProteomePublic HealthPublishingRNA VirusesReagentReportingResolutionRoleSentinelSerial PassageSeriesStructureSymptomsTestingTicksTimeTropismUgandaValidationViral ProteinsVirusVirus DiseasesWest Nile virusYellow fever virusZika Virusbasecyanine dye 5fetalforestimprovedin vivoinduced pluripotent stem cellnerve stem cellnew therapeutic targetnovel therapeuticsnovel vaccinespathogenprogenitorprotein protein interactionpublic health emergencysuccesstherapeutic targettranscriptome sequencingvirus host interactionyeast protein
中文摘要
寨卡病毒(ZIKV)是一种蚊媒黄病毒,据报道目前在26个国家和地区传播,
拉丁美洲和加勒比。虽然感染者通常没有症状或只有轻微的
症状,新出现的证据开始将ZIKV感染与胎儿和新生儿小头畸形联系起来,
神经系统并发症,如格林-巴利综合征。世界卫生组织宣布,
2016年2月1日国际关注。尽管ZIKV的结构、嗜性和发病机制在很大程度上是未知的,
尽管目前还不清楚,但最近的几项研究开始揭示这种病毒的病因。事实上,最近的研究
Ming及其同事发表的研究表明,ZIKV特异性感染人类神经元祖细胞。
下一个重要的步骤是阐明ZIKV-宿主相互作用的分子机制。已经充分
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,物理
与宿主蛋白质接触。因此,构建ZIKV-宿主蛋白质-蛋白质相互作用网络将极大地
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,以确定新的
治疗目标具体而言,我们计划:1)构建ZIKV和DENV-宿主蛋白-蛋白相互作用
2)预测哪些宿主因素在ZIKV-宿主相互作用中起重要作用;以及3)重新评估
使用基于细胞的方法鉴定ZIKV宿主PPI。该项目的成功将为我们提供一个全球PPI
ZIKV和人类蛋白质组之间的网络。ZIKV-host和DENV-host PPI网络之间的比较
将提高我们识别重要宿主因子和/或通常被利用的途径的可能性
被黄病毒感染我们相信,PPI数据集将成为识别新的
这将极大地促进新疗法和疫苗的开发。
英文摘要
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.
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会议论文
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资助金额:$54.74万
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批准号:9789168
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TCP1: ANALYSIS OF LYSINE MODIFICATION USING PROTEIN MICROARRAYS
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批准号:7724685
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资助金额:$40.14万
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依托单位:
DNA-Binding Activity of Human Transcription Factors
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DNA-Binding Activity of Human Proteins
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依托单位:
DNA-Binding Activity of Human Transcription Factors
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资助金额:$27.87万
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DNA-Binding Activity of Human Proteins
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