MOLECULAR DETERMINANTS OF CELL DEATH BY HIV1

HIV1 导致的细胞死亡的分子决定因素

• 批准号: 2876549
• 负责人: MOHAN SOMASUNDARAN
• 金额: $ 23.74万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 1999-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2876549
• 关键词: HIV infections; cell death; clinical research; helper T lymphocyte; human immunodeficiency virus 1; human subject; laboratory mouse; molecular pathology; provirus; recombinant virus; tissue /cell culture; virus cytopathogenic effect

The PI has isolated HIV-1 viruses from infected humans that, despite relatively high viral loads, do not exhibit evidence of clinical progression. Some of these viruses appear to replicate well in a CD4 lymphocyte single cell killing (CD4-SCK) assay designed by the applicant, but exhibit lower levels of induced cytopathic effects. Other viruses isolated from these individuals replicate comparably but induce greater cytopathic effects in CD4-SCK assay. The PI proposes: (1) To generate molecular proviral clones of these HIV-1 isolates that duplicate the observed phenotypes with respect to cell killing; (2) To use recombinant viruses constructed between cytopathic and noncytopathic variants to identify the molecular determinants of cytopathic effect in the CD4-SCK assay and in a NOD/LtSz-scid mouse model. (3) To determine the potential significance of the identified cytopathic determinant in the course of pathogenesis in the non-progressor patients.

PI 已从感染者身上分离出 HIV-1 病毒，尽管 病毒载量相对较高，没有表现出临床证据 进展。 其中一些病毒似乎在 CD4 中复制良好 淋巴细胞单细胞杀伤 (CD4-SCK) 检测由 申请人，但表现出较低水平的诱导细胞病变效应。 从这些个体中分离出的其他病毒的复制能力相当，但是 在 CD4-SCK 测定中诱导更大的细胞病变效应。 PI 建议： (1) 生成这些 HIV-1 分离株的分子原病毒克隆 复制观察到的细胞杀伤表型； (2) 至 使用在细胞病变和非细胞病变之间构建的重组病毒 变体来鉴定细胞病变效应的分子决定因素 CD4-SCK 测定和 NOD/LtSz-scid 小鼠模型。 (3) 确定 所鉴定的细胞病变决定簇的潜在意义 非进展患者的发病机制过程。