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:
    8169121
  • 负责人:
  • 金额:
    $ 4.65万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2010
  • 资助国家:
    美国
  • 起止时间:
    2010-03-01 至 2011-02-28
  • 项目状态:
    已结题

项目摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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 prepared two additional manuscrpts in which immunoisolation mass spectrometry was used to gain clues as to the function of viral proteins in their hosts (see below)
这个子项目是众多研究子项目之一

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)

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THOMAS E SHENK其他文献

THOMAS E SHENK的其他文献

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{{ 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:
    $ 4.65万
  • 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:
    $ 4.65万
  • 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:
    $ 4.65万
  • 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:
    8361504
  • 财政年份:
    2011
  • 资助金额:
    $ 4.65万
  • 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:
    $ 4.65万
  • 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:
    $ 4.65万
  • 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:
    $ 4.65万
  • 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:
    $ 4.65万
  • 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:
    $ 4.65万
  • 项目类别:
PROJECT 3
项目3
  • 批准号:
    7905601
  • 财政年份:
    2009
  • 资助金额:
    $ 4.65万
  • 项目类别:

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