MOLECULAR DETERMINANTS OF CELL DEATH BY HIV1

PI已经从受感染的人身上分离出HIV-1病毒，尽管 相对较高的病毒载量，没有表现出临床证据 进步。其中一些病毒似乎在CD4中复制得很好 淋巴细胞单细胞杀伤(CD4-SCK)试验 申请人，但表现出较低水平的诱导细胞病变效应。 从这些人身上分离出的其他病毒复制能力相似，但 在CD4-SCK实验中诱导更大的细胞病变效应。私隐专员建议： (1)产生这些HIV-1分离株的分子前病毒克隆 复制观察到的细胞杀伤表型；(2) 使用在细胞性和非细胞性之间构建的重组病毒 用于鉴定细胞病变效应的分子决定因素的变体 在NOD/LtSz-SCID小鼠模型中。(三)确定 已确定的细胞病变决定因素在临床中的潜在意义 非进展型患者的发病过程。

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.