Proteins Mediating Interaction of HIV-1 and JCV in CNS
介导中枢神经系统中 HIV-1 和 JCV 相互作用的蛋白质
基本信息
- 批准号:6701819
- 负责人:
- 金额:$ 37.59万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1996
- 资助国家:美国
- 起止时间:1996-02-01 至 2007-01-31
- 项目状态:已结题
- 来源:
- 关键词:AIDS /HIV neuropathyPolyomavirus hominis 2central nervous systemcyclinselectron microscopygene expressiongenetic transcriptiongenomegliahuman immunodeficiency virus 1human tissuelatent virus infectionmolecular geneticsneurotropic virusoligodendrogliapoint mutationpostmortemprogressive multifocal leukoencephalopathyprotein structure functionvirus RNAvirus geneticsvirus infection mechanismvirus proteinvirus replicationvirus virus interaction
项目摘要
DESCRIPTION: (provided by applicant) JC virus (JCV) is the etiologic agent of
the neurodegenerative disease, progressive multifocal leukoencephalopathy
(PML). JCV is normally latent in non-immunocompromised people, but it is
activated in brains of individuals with AIDS. Because of the high incidence of
PML in AIDS, we have hypothesized that activation of JCV in glial cells of the
brain is influenced by HIV-1 infection. We have found that JCV late gene
transcription is stimulated by the HIV-1 Tat protein through action at sequence
elements bound by the cellular protein, Pur about. Tat and Pur0 about form a
highly specific complex, and this complex acts to stimulate transcription at
both the HW-1 TAR RNA element and the JCV late promoter. The complex also
interacts with T-antigen to enhance JCV DNA replication. Purc about is a
frequent partner of cyclin/CDK complexes, as is another Tat-binding protein,
cyclin T1. This proposal aims to continue to exploit the expertise of two
independent laboratories to coordinate studies on HIV-1, JCV and cellular
proteins, including Pur0 about and cyclin T1. We shall take advantage of rapid
autopsy procedures at the Manhattan HIV Brain Bank to perform immunogold
electron microscopy on PML brain samples to colocalize Tat with these cellular
proteins. We shall elucidate the dynamics of the interactions between Tat,
T-antigen and Puro about during the course of JCV infection of oligodendrocytes
and determine whether transcriptional activation involves activity of cyclin
T1/CDK9. We shall characterize the involvement of Purc about or cyclin T1/CDK9
in Tat activation of transcription at TAR(+) or TAR(-) HIV-1 LTR promoters. Use
of Puro about point mutants in AA V vectors will help dissect the contributions
of different molecular unctional groups to HIV-1 replication in
microglial/monocytic cells. We shall pursue our finding that exogenous Tat at
low concentrations is incorporated by KG-1 oligodendrocytes and stimulates DNA
replication initiated at the JCV origin. We shall determine the mechanism by
which Tat enhances replication initiated at the JCV origin in human
oligodendrocytes both in vivo and using a new in vitro system. Results will
help elucidate pathways of activation of HIV-1 and JCV in the brain and will
help target particular molecular interactions for therapy.
描述:(由申请人提供)JC病毒(JCV)是
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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EDWARD M. JOHNSON其他文献
EDWARD M. JOHNSON的其他文献
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{{ truncateString('EDWARD M. JOHNSON', 18)}}的其他基金
PROTEINS MEDIATING INTERACTION OF HIV 1 AND JCV IN CNS
介导中枢神经系统中 HIV 1 和 JCV 相互作用的蛋白质
- 批准号:
2274338 - 财政年份:1996
- 资助金额:
$ 37.59万 - 项目类别:
Proteins Mediating Interaction of HIV-1 and JCV in CNS
介导中枢神经系统中 HIV-1 和 JCV 相互作用的蛋白质
- 批准号:
7382577 - 财政年份:1996
- 资助金额:
$ 37.59万 - 项目类别:
PROTEINS MEDIATING INTERACTION OF HIV 1 AND JCV IN CNS
介导中枢神经系统中 HIV 1 和 JCV 相互作用的蛋白质
- 批准号:
2655530 - 财政年份:1996
- 资助金额:
$ 37.59万 - 项目类别:
Proteins Mediating Interaction of HIV-1 and JCV in CNS
介导中枢神经系统中 HIV-1 和 JCV 相互作用的蛋白质
- 批准号:
6855712 - 财政年份:1996
- 资助金额:
$ 37.59万 - 项目类别:
Proteins Mediating Interaction of HIV-1 and JCV in CNS
介导中枢神经系统中 HIV-1 和 JCV 相互作用的蛋白质
- 批准号:
6450231 - 财政年份:1996
- 资助金额:
$ 37.59万 - 项目类别:
PROTEINS MEDIATING INTERACTION OF HIV 1 AND JCV IN CNS
介导中枢神经系统中 HIV 1 和 JCV 相互作用的蛋白质
- 批准号:
2873191 - 财政年份:1996
- 资助金额:
$ 37.59万 - 项目类别:
Proteins Mediating Interaction of HIV-1 and JCV in CNS
介导中枢神经系统中 HIV-1 和 JCV 相互作用的蛋白质
- 批准号:
6622545 - 财政年份:1996
- 资助金额:
$ 37.59万 - 项目类别:
Proteins Mediating Interaction of HIV-1 and JCV in CNS
介导中枢神经系统中 HIV-1 和 JCV 相互作用的蛋白质
- 批准号:
7991800 - 财政年份:1996
- 资助金额:
$ 37.59万 - 项目类别:
Proteins Mediating Interaction of HIV-1 and JCV in CNS
介导中枢神经系统中 HIV-1 和 JCV 相互作用的蛋白质
- 批准号:
7197830 - 财政年份:1996
- 资助金额:
$ 37.59万 - 项目类别:
PROTEINS MEDIATING INTERACTION OF HIV 1 AND JCV IN CNS
介导中枢神经系统中 HIV 1 和 JCV 相互作用的蛋白质
- 批准号:
2333042 - 财政年份:1996
- 资助金额:
$ 37.59万 - 项目类别:














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