Mitochondrial-localized activities of HHV-8 vIRF-1
Mitochondrial-localized activities of HHV-8 vIRF-1
批准号:
8282293
负责人:
John Nicholas
金额:
$24.6万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2012
资助国家:
美国
项目状态:
已结题
起止时间:
2012-02-01 至 2014-01-31
关键词:
Antiviral AgentsApoptosisApoptoticBH3 DomainBindingBiologicalBiological AssayBiologyCell Cycle ArrestCellsCessation of lifeDataDevelopmentEP300 geneEndothelial CellsFutureGoalsHomologous GeneHuman Herpesvirus 8Immune responseIn VitroIndividualInfectionInterferonsMapsMediatingMembrane ProteinsMitochondriaMitochondrial ProteinsMolecularMutagenesisNuclearNuclear TranslocationPathway interactionsPeptidesPeripheralPropertyProtein Binding DomainProtein FamilyProteinsResearchRoleSiteSpecific qualifier valueSpecificityStimulusStressVariantViralViral ProteinsVirusVirus DiseasesVirus Replicationbasecell growth regulationgain of functiongenetic regulatory proteinin vivoloss of functionmembermutantnoveloverexpressionpro-apoptotic proteinresearch studyresponsetranscription factorviral interferon regulatory factorviral resistance
中文摘要
描述(由申请人提供):人疱疹病毒8 (HHV-8)指定四种病毒干扰素调节因子同源物(vIRFs 1-4),其功能是抑制细胞IRFs以及其他细胞防御途径的成分,这些途径促进细胞周期阻滞和细胞凋亡,以响应病毒感染。被vIRF-1抑制的细胞蛋白包括p53、ATM、GRIM19、Smad转录因子和irf介导应答所需的p300/CBP转录共激活因子。我们已经确定了一种全新的相互作用,在vIRF-1和应激反应,促凋亡的bh3蛋白(BOPs) Bim和Bid之间。vIRF-1与Bim和Bid的相互作用发生在病毒蛋白的残基170-187 (bop结合域,BBD)和BOPs的功能BH3结构域。Bim和Bid都是在HHV-8高产复制过程中被诱导的,它们都被vIRF-1关联在功能上抑制,我们已经确定了vIRF-1在线粒体的部分定位,与
英文摘要
DESCRIPTION (provided by applicant): Human herpesvirus 8 (HHV-8) specifies four viral interferon regulatory factor homologues (vIRFs 1-4) that function to inhibit cellular IRFs in addition to other components of cellular defense pathways that promote cell cycle arrest and apoptosis in response to virus infection. Cellular proteins targeted for inhibition by vIRF-1 include p53, ATM, GRIM19, Smad transcription factors, and p300/CBP transcriptional co-activators required for IRF-mediated responses. We have identified an entirely novel class of interaction, between vIRF-1 and stress-responsive, pro-apoptotic BH3-only proteins (BOPs) Bim and Bid. Interactions of vIRF-1 with Bim and Bid occur via residues 170-187 (BOP-binding domain, BBD) of the viral protein and the functional BH3 domains of the BOPs. Both Bim and Bid are induced during HHV-8 productive replication, each is inhibited functionally by vIRF-1 association, and we have identified partial localization of vIRF-1 to mitochondria, consistent with
the hypothesis that direct targeting and inactivation of BOPs at their site of action is biologicaly important. For Bim, a demonstrated powerful negative regulator of HHV-8 replication, we have also shown that vIRF-1 binding leads to nuclear translocation, representing a secondary mode of inactivation. These properties of vIRF-1 represent new paradigms of viral control of host responses to infection. This application is focused on examining: (1) the structural requirements of vIRF-1 mitochondrial localization and associated activities; (2) the molecular basis of BOP/BH3 targeting by vIRF-1; (3) the functional significance of individual vIRF-1:BOP interactions and of vIRF-1 mitochondrial localization in HHV-8 biology. The project will characterize unique properties and activities of vIRF-1, thereby expand understanding of viral evasion from host cell defenses, and potentially enabling future development of novel antiviral agents.
PUBLIC HEALTH RELEVANCE: Human herpesvirus 8 (HHV-8) encodes an interferon regulatory factor homologue, vIRF-1, that contributes to viral resistance to innate host cell defenses against viral infection. We have identified a novel mechanism of vIRF-1 function, namely the direct binding to and inhibition of cellular pro-death proteins (BH3- only proteins, BOPs), which are known to be critically important as negative regulators of virus replication. The goal of the proposed research is to elucidate the molecular determinants and mechanisms of BOP recognition and inactivation by vIRF-1, thereby characterizing this previously unknown means of virus manipulation of host cell responses to infection.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
USP7 targeting by HHV-8 vIRFs
-
批准号:9883702
-
项目类别:
-
资助金额:$40.94万
-
财政年份:2019
-
负责人:John Nicholas
-
依托单位:
USP7 targeting by HHV-8 vIRFs
-
批准号:10361554
-
项目类别:
-
资助金额:$40.94万
-
财政年份:2019
-
负责人:John Nicholas
-
依托单位:
USP7 targeting by HHV-8 vIRFs
-
批准号:10581544
-
项目类别:
-
资助金额:$40.94万
-
财政年份:2019
-
负责人:John Nicholas
-
依托单位:
HHV-8 vIRF interactions in the context of infection
-
批准号:8994365
-
项目类别:
-
资助金额:$17.62万
-
财政年份:2015
-
负责人:John Nicholas
-
依托单位:
HHV-8 vIRF interactions in the context of infection
-
批准号:9085244
-
项目类别:
-
资助金额:$21.14万
-
财政年份:2015
-
负责人:John Nicholas
-
依托单位:
Inhibitory targeting of HHV-8 vIL-6-related interactions.
-
批准号:8595304
-
项目类别:
-
资助金额:$20.51万
-
财政年份:2013
-
负责人:John Nicholas
-
依托单位:
BH3-only protein targeting by HHV-8
-
批准号:9193611
-
项目类别:
-
资助金额:$40.5万
-
财政年份:2013
-
负责人:John Nicholas
-
依托单位:
BH3-only protein targeting by HHV-8
-
批准号:8537068
-
项目类别:
-
资助金额:$38.07万
-
财政年份:2013
-
负责人:John Nicholas
-
依托单位:
Inhibitory targeting of HHV-8 vIL-6-related interactions.
-
批准号:8467210
-
项目类别:
-
资助金额:$17.62万
-
财政年份:2013
-
负责人:John Nicholas
-
依托单位:
BH3-only protein targeting by HHV-8
-
批准号:8601429
-
项目类别:
-
资助金额:$40.5万
-
财政年份:2013
-
负责人:John Nicholas
-
依托单位:
BH3-only protein targeting by HHV-8
-
批准号:8786056
-
项目类别:
-
资助金额:$40.5万
-
财政年份:2013
-
负责人:John Nicholas
-
依托单位:
Activities of HHV-8 vIRF-1 in Virus Biology
-
批准号:8508375
-
项目类别:
-
资助金额:$40.5万
-
财政年份:2012
-
负责人:John Nicholas
-
依托单位:
Mitochondrial-localized activities of HHV-8 vIRF-1
-
批准号:8413784
-
项目类别:
-
资助金额:$20.5万
-
财政年份:2012
-
负责人:John Nicholas
-
依托单位:
Role of vGPCR in HHV-8 productive replication
-
批准号:8107969
-
项目类别:
-
资助金额:$41.0万
-
财政年份:2010
-
负责人:John Nicholas
-
依托单位:
Bim regulation by HHV-8 vIRF-1
-
批准号:7554328
-
项目类别:
-
资助金额:$18.45万
-
财政年份:2008
-
负责人:John Nicholas
-
依托单位:
Bim regulation by HHV-8 vIRF-1
-
批准号:7667943
-
项目类别:
-
资助金额:$22.14万
-
财政年份:2008
-
负责人:John Nicholas
-
依托单位:
HHV-8 vGPCR Signaling in Virus Biology
-
批准号:7228721
-
项目类别:
-
资助金额:$16.38万
-
财政年份:2007
-
负责人:John Nicholas
-
依托单位:
HHV-8 vGPCR Signaling in Virus Biology
-
批准号:7343218
-
项目类别:
-
资助金额:$19.68万
-
财政年份:2007
-
负责人:John Nicholas
-
依托单位:
P-3:Viral Chemokine signalling in HHV-8 infection
-
批准号:7065941
-
项目类别:
-
资助金额:$17.75万
-
财政年份:2005
-
负责人:John Nicholas
-
依托单位:
ROLE OF VIL-6 IN PRIMARY EFFUSION LYMPHOMAS
-
批准号:6514205
-
项目类别:
-
资助金额:$18.39万
-
财政年份:2000
-
负责人:John Nicholas
-
依托单位:
国内基金
海外基金
登录
查看更多内容
Epac1/2通过蛋白酶体调控中性粒细胞NETosis和Apoptosis在急性肺损伤中的作用研究
-
批准号:LBY21H010001
-
项目类别:省市级项目
-
资助金额:--
-
批准年份:2020
-
负责人:郑绪阳
-
依托单位:
基于Apoptosis/Ferroptosis双重激活效应的天然产物AlbiziabiosideA的抗肿瘤作用机制研究及其结构改造
-
批准号:81703335
-
项目类别:青年科学基金项目
-
资助金额:20.0万元
-
批准年份:2017
-
负责人:卫高菲
-
依托单位:
双肝移植后Apoptosis和pyroptosis在移植物萎缩差异中的作用和供受者免疫微环境变化研究
-
批准号:81670594
-
项目类别:面上项目
-
资助金额:58.0万元
-
批准年份:2016
-
负责人:陈昊
-
依托单位:
Serp-2 调控apoptosis和pyroptosis 对肝脏缺血再灌注损伤的保护作用研究
-
批准号:81470791
-
项目类别:面上项目
-
资助金额:73.0万元
-
批准年份:2014
-
负责人:董家鸿
-
依托单位:
Apoptosis signal-regulating kinase 1是七氟烷抑制小胶质细胞活化的关键分子靶点?
-
批准号:81301123
-
项目类别:青年科学基金项目
-
资助金额:23.0万元
-
批准年份:2013
-
负责人:王海莲
-
依托单位:
APO-miR(multi-targeting apoptosis-regulatory miRNA)在前列腺癌中的表达和作用
-
批准号:81101529
-
项目类别:青年科学基金项目
-
资助金额:22.0万元
-
批准年份:2011
-
负责人:陈雪芹
-
依托单位:
放疗与细胞程序性死亡(APOPTOSIS)相关性及其应用研究
-
批准号:39500043
-
项目类别:青年科学基金项目
-
资助金额:9.0万元
-
批准年份:1995
-
负责人:梁克
-
依托单位: