PATHOGENESIS OF HIV INDUCED IMMUNODEFICIENCY

HIV 引起的免疫缺陷的发病机制

• 批准号: 2873741
• 负责人: ASHLEY T. HAASE
• 金额: $ 32.2万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-03-01 至 2004-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2873741
• 关键词: AIDS; CD4 molecule; HIV infections; bone marrow; cell population study; gene expression; genetic manipulation; genome; helper T lymphocyte; host organism interaction; human immunodeficiency virus; human subject; immunochemistry; in situ hybridization; lymph nodes; lymphatic system; nucleic acid probes; single cell analysis; virus DNA; virus antigen; virus cytopathogenic effect

This proposal is directed to the molecular pathogenesis of infection by the human immunodeficiency virus (HIV) and in particular to the basis for its cardinal manifestation, the acquired immuno deficiency syndrome (AIDS). We describe longitudinal analyses of lymph node and bone marrow by in situ hybridization and cognate single cells methods to define the number and type of cells which harbor HIV, and the extent of virus gene expression vis-a-vis viral and regulatory genes and stage of disease. We think this analysis will provide support for a war of attrition hypothesis which accounts for the profound loss of T helper lymphocytes despite the relatively low frequency of cells in which viral RNA can be demonstrated. We also will look for a mutant virulent virus in the later stages of disease. If one is found we will characterize the genome of the virus for comparisons with earlier isolates with the aim of identifying viral genes with a critical role in pathogenesis.

该建议针对 人类免疫缺陷病毒（HIV）感染 特定于其基本表现的基础， 获得的免疫缺陷综合征（AIDS）。 我们描述 原位对淋巴结和骨髓的纵向分析 杂交和同源单细胞方法来定义数字 和含有HIV的细胞类型以及病毒基因的程度 相对于病毒和调节基因的表达以及 疾病。 我们认为此分析将为战争提供支持 损耗假设是t的深刻损失 助手淋巴细胞尽管细胞的频率相对较低 可以证明病毒RNA。 我们还将寻找 在疾病后期的突变毒病毒。 如果是 发现我们将表征病毒的基因组以进行比较 较早的分离株，目的是鉴定具有 在发病机理中的关键作用。