淋巴细胞HI V-1辅受体的表型剔除对病毒感染的阻断作用

批准号:
39970695
项目类别:
面上项目
资助金额:
10.0 万元
负责人:
白雪帆
依托单位:
学科分类:
C0807.生殖免疫与移植免疫
结题年份:
2002
批准年份:
1999
项目状态:
已结题
项目参与者:
黄长形、潘蕾、傅恩清、康文臻、李光玉
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中文摘要
AI DS 是严重危害人类健康的疾病,其化疗目前仍无突破性进展,各种基因治疗也举步为琛P陆⑾值那骰蜃邮芴錍X CR -4和CC R-5是HI V-1感染重要的辅受体。本研究拟通齛和类趋化因子SD F与RAN TES的细胞内表达以及表达产物与HI V-1 辅受体的结合,从细胞表型上剔除两类辅受体,从而实现同时阻断两种嗜性病毒感染的目的,为AI DS 的治疗开偾椎耐揪丁
英文摘要
We utilized a novel intracellular chemokine(intrakine) strategy to co-inactivate genetically both CCR-5 and CXCR-4 in human lymphocytes. The principle of co-inactivation of CCR-5 and CXCR-4 was illustrated by targeting the CC-intrakine and CXC-intrakine to the lumen of the endoplasmic reticulum (ER) for intracellular blockade of the transport of newly synthesized chemokine coreceptors to the cell surface. We constructed bicistronic vectors for CC-intrakine and CXC-intrakine and examined co-expression of them. The lymphocytes with the phenotypic knock-out of CCR-5 and CXCR-4 were found broadly resist the infection of M-tropic, T-tropic and dual-tropic HIV-1 viruses. Moreover, the transduced lymphocytes retained normal cell features, including the responsiveness to mitogen and recall antigen stimulation. Thus, this study demonstrates that genetic co-inactivation of the M- and T-tropic HIV-1 principal coreceptors in lymphocytes or other cells could be a viable strategy for the long-term control of HIV-1 infection.
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专利列表
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- 批准号:30872215
- 项目类别:面上项目
- 资助金额:33.0万元
- 批准年份:2008
- 负责人:白雪帆
- 依托单位:
汉滩病毒G1蛋白ITAM样基序在HFRS免疫信号传递中的作用及其与血管内皮损伤的关系
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- 项目类别:面上项目
- 资助金额:21.0万元
- 批准年份:2004
- 负责人:白雪帆
- 依托单位:
抗汉滩病毒人源抗体基因的克隆与表达
- 批准号:39370619
- 项目类别:面上项目
- 资助金额:5.0万元
- 批准年份:1993
- 负责人:白雪帆
- 依托单位:
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