FOLLOWING THE FATE OF HCMV GENE PRODUCTS IN HOST CELLS
追踪 HCMV 基因产物在宿主细胞中的命运
基本信息
- 批准号:8361504
- 负责人:
- 金额:$ 0.65万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2011
- 资助国家:美国
- 起止时间:2011-03-01 至 2012-03-31
- 项目状态:已结题
- 来源:
- 关键词:AdultAge-YearsApoptosisCellsCellular StressCharacteristicsCollaborationsComplexCytomegalovirusCytomegalovirus InfectionsEarly PromotersEpitopesExhibitsFundingGeographic LocationsGrantHerpesviridaeInfectionJournalsLaboratoriesManuscriptsMass Spectrum AnalysisMicrobeNational Center for Research ResourcesNuRD complexPathway interactionsPrincipal InvestigatorProtein BiosynthesisProteinsPublishingRNAResearchResearch InfrastructureResourcesSignal TransductionSourceStagingStressT-LymphocyteTSC1 geneTSC1/2 geneTSC2 geneTuberous SclerosisTuberous sclerosis protein complexTumor Suppressor ProteinsUnited StatesUnited States National Institutes of HealthUniversitiesViralViral GenomeViral PhysiologyViral ProteinsVirus ReplicationWorkbiological adaptation to stresscell growthcostinsightmTOR proteinmacromoleculepathogenpreventprotein complexresponsesocioeconomicsvirology
项目摘要
This subproject is one of many research subprojects utilizing the resources
provided by a Center grant funded by NIH/NCRR. Primary support for the subproject
and the subproject's principal investigator may have been provided by other sources,
including other NIH sources. The Total Cost listed for the subproject likely
represents the estimated amount of Center infrastructure utilized by the subproject,
not direct funding provided by the NCRR grant to the subproject or subproject staff.
Cytomegalovirus is widely spread throughout all geographic locations and socioeconomic group and infects 85% of adults in United States by 40 years of age. Our aim is to study the interactions of human cytomegalovirus with cellular proteins, and gain insights into cellular pathways modulated by herpesviruses. This study was initiated one and a half years ago in collaboration with the laboratory of Tom Shenk at Princeton University. Since then, we have isolated a variety of Protein A- or GFP-tagged HCMV viral proteins identifying their host and viral interacting partners at various stages of infections. During this last year, we have studied the interacting partners of several viral proteins, including UL83, UL121, UL38, UL99, and US22. Each of these studies highlighted new ways that HCMV utilizes to manipulate and take over the cell.
Human cytomegalovirus proteins alter host cells to favor virus replication. These viral proteins include pUL38, which prevents apoptosis. To characterize the mode of action of pUL38, we modified the viral genome to encode an epitope-tagged pUL38 and used rapid immunoaffinity purification to isolate pUL38-interacting host proteins, which were then identified by mass spectrometry. One of the cellular proteins identified was TSC2, a constituent of the tuberous sclerosis tumor suppressor protein complex (TSC1/2). TSC1/2 integrates stress signals and regulates the mammalian target of rapamycin complex 1 (mTORC1), a protein complex that responds to stress by limiting protein synthesis and cell growth. We showed that pUL38 interacts with TSC1 and TSC2 in cells infected with wild-type cytomegalovirus. Furthermore, TSC1/2 failed to regulate mTORC1 in cells expressing pUL38, and these cells exhibited the enlarged size characteristic of cytomegalovirus infection. Thus, pUL38 supports virus replication at least in part by blocking cellular responses to stress. A manuscript describing this work has been published:
Human cytomegalovirus protein UL38 inhibits host cell stress responses by antagonizing the tuberous sclerosis protein complex. Moorman NJ, Cristea IM, Terhune SS, Rout MP, Chait BT, Shenk T. Cell Host Microbe. 2008 3(4):253-62.
Most recently, we have published two additional manuscripts in which immunoisolation mass spectrometry was used to gain clues as to the function of viral proteins in their hosts:
S.S. Terhune, N.J. Moorman, I.M. Cristea, J.P. Savaryn, C. Cuevas-Bennett1, M.P. Rout, B.T. Chait, T. Shenk Human cytomegalovirus UL29/28 protein interacts with components of the NuRD complex which promote accumulation of immediate-early RNA PLoS Pathogens 6(2010)e1000965.
I.M. Cristea, N.J. Moorman, S.S. Terhune, C.D. Cuevas, E.S. O'Keefe, M.P. Rout, B.T. Chait, T.Shenk Human Cytomegalovirus pUL83 Stimulates Activity of the Viral Immediate-Early Promoter through its Interaction with the Cellular IFI16 Protein Journal of Virology 84(2010)7803-14.
这个子项目是许多利用资源的研究子项目之一
由NIH/NCRR资助的中心拨款提供。子项目的主要支持
而子项目的主要调查员可能是由其他来源提供的,
包括其它NIH来源。 列出的子项目总成本可能
代表子项目使用的中心基础设施的估计数量,
而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。
巨细胞病毒在所有地理位置和社会经济群体中广泛传播,并在美国40岁以下的成年人中感染85%。我们的目的是研究人类巨细胞病毒与细胞蛋白的相互作用,并深入了解疱疹病毒调控的细胞途径。这项研究是在一年半前与普林斯顿大学的Tom Shenk实验室合作发起的。从那时起,我们已经分离出各种蛋白A或GFP标记的HCMV病毒蛋白,在感染的各个阶段鉴定其宿主和病毒相互作用的伴侣。在过去的一年中,我们研究了几种病毒蛋白的相互作用伴侣,包括UL 83,UL 121,UL 38,UL 99和US 22。这些研究中的每一项都强调了HCMV用来操纵和接管细胞的新方法。
人巨细胞病毒蛋白改变宿主细胞以利于病毒复制。这些病毒蛋白包括pUL 38,其防止细胞凋亡。为了表征pUL 38的作用模式,我们修改了病毒基因组以编码表位标记的pUL 38,并使用快速免疫亲和纯化来分离pUL 38相互作用的宿主蛋白,然后通过质谱鉴定。鉴定的细胞蛋白之一是TSC 2,它是结节性硬化症肿瘤抑制蛋白复合物(TSC 1/2)的组成部分。TSC 1/2整合应激信号并调节雷帕霉素复合物1(mTORC 1)的哺乳动物靶标,mTORC 1是一种通过限制蛋白质合成和细胞生长来响应应激的蛋白质复合物。我们发现,pUL 38与TSC 1和TSC 2在感染野生型巨细胞病毒的细胞中相互作用。此外,TSC 1/2不能调节表达pUL 38的细胞中的mTORC 1,并且这些细胞表现出巨细胞病毒感染的特征性的增大的尺寸。因此,pUL 38至少部分通过阻断细胞对应激的反应来支持病毒复制。描述这项工作的手稿已经出版:
人巨细胞病毒蛋白UL 38通过拮抗结节性硬化症蛋白复合物抑制宿主细胞应激反应。Moorman NJ,Cristea IM,Terhune SS,Rout MP,Chait BT,Shenk T.细胞宿主微生物。2008 3(4):253-62.
最近,我们发表了另外两篇手稿,其中使用免疫隔离质谱法来获得关于病毒蛋白在其宿主中的功能的线索:
S.S. Terhune,N.J. Moorman,I.M. Cristea,J.P. Savaryn,C. Cuevas-Bennett 1,M.P. Rout,B.T. Chait,T. Shenk人巨细胞病毒UL 29/28蛋白与NuRD复合物的组分相互作用,促进立即早期RNA的积累PLoS Pathogens 6(2010)e1000965。
I.M. Cristea,N.J. Moorman,S.S.特胡恩角奎瓦斯O'Keefe,M.P. Rout,B.T. Chait,T.Shenk Human Cytomegalovirus pUL83 Stimulates Activity of the Viral Immediate-Early Promoter through its Interaction with the Cellular IFI16 Protein Journal of Virology 84(2010)7803-14.
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
THOMAS E SHENK其他文献
THOMAS E SHENK的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('THOMAS E SHENK', 18)}}的其他基金
Human cytomegalovirus-induced alterations to cell-surface adhesion proteins
人巨细胞病毒诱导的细胞表面粘附蛋白改变
- 批准号:
8990958 - 财政年份:2015
- 资助金额:
$ 0.65万 - 项目类别:
Human cytomegalovirus-induced alterations to cell-surface adhesion proteins
人巨细胞病毒诱导的细胞表面粘附蛋白改变
- 批准号:
9195706 - 财政年份:2015
- 资助金额:
$ 0.65万 - 项目类别:
Human cytomegalovirus-induced alterations to cell-surface adhesion proteins
人巨细胞病毒诱导的细胞表面粘附蛋白改变
- 批准号:
8885082 - 财政年份:2015
- 资助金额:
$ 0.65万 - 项目类别:
Human cytomegalovirus latency in cultured monocytes
培养单核细胞中的人巨细胞病毒潜伏期
- 批准号:
8416378 - 财政年份:2010
- 资助金额:
$ 0.65万 - 项目类别:
Human cytomegalovirus latency in cultured monocytes
培养单核细胞中的人巨细胞病毒潜伏期
- 批准号:
7859083 - 财政年份:2010
- 资助金额:
$ 0.65万 - 项目类别:
Human cytomegalovirus latency in cultured monocytes
培养单核细胞中的人巨细胞病毒潜伏期
- 批准号:
8019543 - 财政年份:2010
- 资助金额:
$ 0.65万 - 项目类别:
Human cytomegalovirus latency in cultured monocytes
培养单核细胞中的人巨细胞病毒潜伏期
- 批准号:
8605153 - 财政年份:2010
- 资助金额:
$ 0.65万 - 项目类别:
Human cytomegalovirus latency in cultured monocytes
培养单核细胞中的人巨细胞病毒潜伏期
- 批准号:
8212375 - 财政年份:2010
- 资助金额:
$ 0.65万 - 项目类别:
FOLLOWING THE FATE OF HCMV GENE PRODUCTS IN HOST CELLS
追踪 HCMV 基因产物在宿主细胞中的命运
- 批准号:
8169121 - 财政年份:2010
- 资助金额:
$ 0.65万 - 项目类别:
相似海外基金
PREDICTING CARIES RISK IN UNDERSERVED CHILDREN, FROM TODDLERS TO THE SCHOOL-AGE YEARS, IN PRIMARY HEALTHCARE SETTINGS
预测初级医疗保健机构中从幼儿到学龄儿童的龋齿风险
- 批准号:
10361268 - 财政年份:2021
- 资助金额:
$ 0.65万 - 项目类别:
Predicting Caries Risk in Underserved Children, from Toddlers to the School-Age Years, in Primary Healthcare Settings
预测初级医疗机构中服务不足的儿童(从幼儿到学龄儿童)的龋齿风险
- 批准号:
9751077 - 财政年份:2011
- 资助金额:
$ 0.65万 - 项目类别:
Predicting Caries Risk in Underserved Children, from Toddlers to the School-Age Years, in Primary Healthcare Settings
预测初级医疗机构中服务不足的儿童(从幼儿到学龄儿童)的龋齿风险
- 批准号:
10457019 - 财政年份:2011
- 资助金额:
$ 0.65万 - 项目类别:
Predicting Caries Risk in Underserved Children, from Toddlers to the School-Age Years, in Primary Healthcare Settings
预测初级医疗机构中服务不足的儿童(从幼儿到学龄儿童)的龋齿风险
- 批准号:
9976990 - 财政年份:2011
- 资助金额:
$ 0.65万 - 项目类别:
Predicting Caries Risk in Underserved Children, from Toddlers to the School-Age Years, in Primary Healthcare Settings
预测初级医疗机构中服务不足的儿童(从幼儿到学龄儿童)的龋齿风险
- 批准号:
10213006 - 财政年份:2011
- 资助金额:
$ 0.65万 - 项目类别: