Active Movement of Immune Cells Away From HIV-1 gp120
免疫细胞主动运动远离 HIV-1 gp120
基本信息
- 批准号:6511570
- 负责人:
- 金额:$ 34.6万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2001
- 资助国家:美国
- 起止时间:2001-04-01 至 2006-03-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
DESCRIPTION: (provided by applicant) The incidence of HIV-1 infection continues
to rise in populations throughout the world despite the development of
candidate vaccines and highly active anti-retroviral therapy (I-IAART). It is
now clear that HIV- I establishes a chronic infection in humans which the host
immune system fails to eradicate despite the presence of HI V-specific cell
mediated and humoral immune responses. HIV- 1 exploits various mechanisms in
order to evade the immune system including the infection and killing of
HIV-specific helper T-cells, the maintenance of a latent state and mutation of
its immunogenic envelope protein, gp120. We propose that HIV-1 proteins such as
gp120 interfere with immune cell migration allowing HIV-infected cells to
escape challenge by host immune effector cells. We have recently demonstrated
that resting T-cells move away from the chemokine, stromal-cell derived
factor-I (SDF-1) and HIV-1IIIB gp120, in a CXCR4 receptor mediated and
concentration dependent manner in vitro and in vivo. In addition, we showed
that the intracellular signaling pathway for movement of resting T-cells away
from both SDF-1 or HIV-1 gp120 was distinct from that for movement towards the
chemokinetic agents. In view of these preliminary findings we intend to define
the migratory responses to HIV-1 gp120 of immune effector cells which are known
to be directly involved in the immune control of HJV infection in vivo. In this
way we would propose to determine whether movement of immune effector cells
away from HIV-1gp120 contributes to a novel mechanism by which HIV-1 evades the
immune system. The proposal has three aims; 1) The characterization of the
migratory response of activated T-cells, including HI V-specific cytotoxic
lymphocytes (CTLs), and monocytes away from CCR5 binding chemokines and CCR5
binding HIV-1 gp120 using a number of established in vitro transmigration
assays. 2) The biochemical characterization of the migration of immune effector
cells away from CCR5 binding HIV-1 gp120 using a battery of signal transduction
pathway inhibitors, mutants of the gp120 molecule and antibodies directed
against gp120 and its chemokine co-receptor binding site 3). The definition of
the role of HIV-l gp120 induced modulation of immune effector cell migration in
vivo using animal model systems in which HIV-1 gp120 is expressed and
modulation of the immune response to the WV -1 protein is quantitated. In these
ways we hope to expand the understanding of why humans fail to contain HIV- 1
infection and to facilitate the design of novel therapies that will ultimately
assist in the eradication of the virus in the HI V-infected individual.
描述:(由申请人提供)HIV-1感染的发生率继续上升
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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MARK Coleman POZNANSKY其他文献
MARK Coleman POZNANSKY的其他文献
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{{ truncateString('MARK Coleman POZNANSKY', 18)}}的其他基金
HIV-1 gp120 induced CTL chemorepulsion:dysregulation of migration & localization
HIV-1 gp120诱导的CTL化学排斥:迁移失调
- 批准号:
8141673 - 财政年份:2010
- 资助金额:
$ 34.6万 - 项目类别:
HIV-1 gp120 induced CTL chemorepulsion:dysregulation of migration & localization
HIV-1 gp120诱导的CTL化学排斥:迁移失调
- 批准号:
7900116 - 财政年份:2009
- 资助金额:
$ 34.6万 - 项目类别:
Movement of Recipient T-Cells Away From an Allograft
受体 T 细胞远离同种异体移植物的运动
- 批准号:
6352372 - 财政年份:2001
- 资助金额:
$ 34.6万 - 项目类别:
Active Movement of Immune Cells Away From HIV-1 gp120
免疫细胞主动运动远离 HIV-1 gp120
- 批准号:
6717680 - 财政年份:2001
- 资助金额:
$ 34.6万 - 项目类别:
Active Movement of Immune Cells Away From HIV-1 gp120
免疫细胞主动运动远离 HIV-1 gp120
- 批准号:
6632464 - 财政年份:2001
- 资助金额:
$ 34.6万 - 项目类别:
Movement of Recipient T-Cells Away From an Allograft
受体 T 细胞远离同种异体移植物的运动
- 批准号:
6534341 - 财政年份:2001
- 资助金额:
$ 34.6万 - 项目类别:
Active Movement of Immune Cells Away From HIV-1 gp120
免疫细胞主动运动远离 HIV-1 gp120
- 批准号:
6348392 - 财政年份:2001
- 资助金额:
$ 34.6万 - 项目类别:
Active Movement of Immune Cells Away From HIV-1 gp120
免疫细胞主动运动远离 HIV-1 gp120
- 批准号:
6867443 - 财政年份:2001
- 资助金额:
$ 34.6万 - 项目类别:
HIV-1 gp120 induced CTL chemorepulsion:dysregulation of migration & localization
HIV-1 gp120诱导的CTL化学排斥:迁移失调
- 批准号:
7465463 - 财政年份:2001
- 资助金额:
$ 34.6万 - 项目类别:
HIV-1 gp120 induced CTL chemorepulsion:dysregulation of migration & localization
HIV-1 gp120诱导的CTL化学排斥:迁移失调
- 批准号:
7662414 - 财政年份:2001
- 资助金额:
$ 34.6万 - 项目类别:
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