TRANSGENIC MICE AS A MODEL TO STUDY HEPATITIS C VIRUS IMMUNOPATHOGENESIS
转基因小鼠作为研究丙型肝炎病毒免疫发病机制的模型
基本信息
- 批准号:6201330
- 负责人:
- 金额:$ 15.66万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1999
- 资助国家:美国
- 起止时间:1999-08-01 至 2000-07-31
- 项目状态:已结题
- 来源:
- 关键词:bone marrow cellular immunity cooperative study cytotoxic T lymphocyte disease /disorder model gene expression genetically modified animals helper T lymphocyte hepatitis C hepatitis C virus laboratory mouse macrophage model design /development passive immunization pathologic process polymerase chain reaction tissue /cell culture tissue mosaicism virus infection mechanism virus protein
项目摘要
The goals of this project are to determine if the expression of the
hepatitis C virus (HCV) core protein alters the ability of the immune
system to cause hepatitis, and results in immune dysfunctions by
altering the ability of the immune system to generate effectors. The
first aim is to determine if expression of the core protein in
hepatocytes alters their ability to be recognized by CD8+ and CD4+
immune effectors. This will be accomplished by adoptive transfer of
NS5-specific immune effectors into transgenic (TG) mice expressing both
NS5 and core protein under the control of a hepatocyte-specific
promoter. These mice will be compared to mice expressing the NS5 gene
only in hepatocytes. The second aim is based on Dr. Lai's data (Project
I) showing the interaction(s) of the core protein with members of the
tumor necrosis factor receptor family. TG mice expressing the core
protein under control of the CMV promoter will be examined for immune
defects related to alterations in receptor signaling. The hypothesis
of the final aim is based on the findings that HCV infects both PBMC and
bone marrow cells. Our hypothesis is that expression of the core
protein in either macrophage antigen presenting cells or the T cells
themselves leads to immune dysregulation. This ability to alter immune
responsiveness facilitates HCV persistence. Tests of this aim
hypothesis will initially use bone marrow chimeras to determine if
expression of the core protein alters immune responsiveness. It will
be pursued by specific expression of the core protein in either
macrophages or in T cells using cell type specific promoters. This
project will establish a small animal model system for studying the
pathogenesis of HCV, which is one of the major goals of this center.
This project interacts closely with Project I.
这个项目的目标是确定是否表达了
丙型肝炎病毒核心蛋白改变机体免疫能力
系统导致肝炎,并通过以下方式导致免疫功能障碍
改变免疫系统产生效应器的能力。这个
第一个目标是确定核心蛋白是否在
肝细胞改变其识别CD8+和CD4+的能力
免疫效应器。这将通过以下方式实现:
NS5特异性免疫效应器在转基因(TG)小鼠中的表达
NS5和核心蛋白控制下的一种肝细胞特异性
推动者。这些小鼠将被与表达NS5基因的小鼠进行比较
只存在于肝细胞中。第二个目标是基于赖博士的数据(项目
I)显示核心蛋白与成员的相互作用(S)
肿瘤坏死因子受体家族。表达核心蛋白的转基因小鼠
在CMV启动子控制下的蛋白质将被检测为免疫
缺陷与受体信号的改变有关。假说
最终目标的基础是丙型肝炎病毒感染PBMC和
骨髓细胞。我们的假设是核心的表达
巨噬细胞抗原提呈细胞或T细胞中的蛋白质
它们本身会导致免疫失调。这种改变免疫力的能力
反应性促进了丙型肝炎病毒的持久性。对这一目标的考验
假说最初将使用骨髓嵌合体来确定
核心蛋白的表达改变了免疫反应性。会的
通过核心蛋白在任一种植物中的特定表达而被追求
巨噬细胞或T细胞中使用细胞类型特异性启动子。这
该项目将建立一个小动物模型系统来研究
丙型肝炎的发病机制,这是该中心的主要目标之一。
该项目与项目I密切互动。
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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GUNTHER DENNERT其他文献
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{{ truncateString('GUNTHER DENNERT', 18)}}的其他基金
REGULATION BY CELL SURFACE RECEPTOR ADP-RIBOSYLATION
细胞表面受体 ADP-核糖基化的调节
- 批准号:
2902173 - 财政年份:1999
- 资助金额:
$ 15.66万 - 项目类别:
REGULATION BY CELL SURFACE RECEPTOR ADP-RIBOSYLATION
细胞表面受体 ADP-核糖基化的调节
- 批准号:
6511085 - 财政年份:1999
- 资助金额:
$ 15.66万 - 项目类别:
REGULATION BY CELL SURFACE RECEPTOR ADP-RIBOSYLATION
细胞表面受体 ADP-核糖基化的调节
- 批准号:
6170658 - 财政年份:1999
- 资助金额:
$ 15.66万 - 项目类别:
REGULATION BY CELL SURFACE RECEPTOR ADP-RIBOSYLATION
细胞表面受体 ADP-核糖基化的调节
- 批准号:
6373987 - 财政年份:1999
- 资助金额:
$ 15.66万 - 项目类别:
FUNCTIONAL ROLES OF GLUCOSE REGULATED PROTEIN GENE SYSTEM IN TARGETED TUMOR
葡萄糖调节蛋白基因系统在靶向肿瘤中的功能作用
- 批准号:
6102897 - 财政年份:1998
- 资助金额:
$ 15.66万 - 项目类别:
FUNCTIONAL ROLES OF GLUCOSE REGULATED PROTEIN GENE SYSTEM IN TARGETED TUMOR
葡萄糖调节蛋白基因系统在靶向肿瘤中的功能作用
- 批准号:
6300449 - 财政年份:1998
- 资助金额:
$ 15.66万 - 项目类别:
TRANSGENIC MICE AS A MODEL TO STUDY HEPATITIS C VIRUS IMMUNOPATHOGENESIS
转基因小鼠作为研究丙型肝炎病毒免疫发病机制的模型
- 批准号:
6100108 - 财政年份:1998
- 资助金额:
$ 15.66万 - 项目类别:
FUNCTIONAL ROLES OF GLUCOSE REGULATED PROTEIN GENE SYSTEM IN TARGETED TUMOR
葡萄糖调节蛋白基因系统在靶向肿瘤中的功能作用
- 批准号:
6237398 - 财政年份:1997
- 资助金额:
$ 15.66万 - 项目类别:
TRANSGENIC MICE AS A MODEL TO STUDY HEPATITIS C VIRUS IMMUNOPATHOGENESIS
转基因小鼠作为研究丙型肝炎病毒免疫发病机制的模型
- 批准号:
6235527 - 财政年份:1997
- 资助金额:
$ 15.66万 - 项目类别:
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