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已从受感染的人类中分离出HIV-1病毒，尽管 病毒载荷相对较高，不显示临床的证据 进展。 这些病毒中的一些似乎在CD4中很好地复制了 由淋巴细胞单细胞杀伤（CD4-SCK）测定 申请人，但表现出较低的诱导细胞质作用。 与这些人隔离的其他病毒复制相当，但 在CD4-SCK分析中诱导更大的细胞质作用。 PI提出： （1）生成这些HIV-1分离株的分子前病毒克隆 复制观察到的表型相对于细胞杀死； （2）至 使用细胞病和非肿瘤之间构建的重组病毒 鉴定细胞疗法的分子决定因素的变体 CD4-SCK分析和NOD/LTSZ-SCID小鼠模型。 （3）确定 已鉴定的细胞质决定因素在 非促进剂患者的发病机理过程。