Differential expression profiles of apoptosis-affecting genes in HIV-infected cell lines and patient T cells.-猫眼课题宝

HIV 感染细胞系和患者 T 细胞中凋亡影响基因的差异表达谱。

DOI：

10.1097/00002030-199902040-00004

发表时间：

1999

期刊：

AIDS (London, England)

影响因子：

通讯作者：

中科院分区：

文献类型：

作者：

Scheuring,UJ;Sabzevari,H;Corbeil,J;Theofilopoulos,AN

目的：阐明HIV诱导的细胞凋亡的分子机制。设计：评估HIV-1 LAI感染的T淋巴母细胞（CEM）细胞以及HIV感染者和对照组的CD 4和CD 8细胞中影响相关细胞周期和凋亡过程的基因的表达模式。方法：通过流式细胞术从报告载体中检测绿色荧光蛋白的表达，确定CEM细胞中HIV感染的动力学。碘化丙啶染色和流式细胞术检测CEM细胞凋亡。结果：感染后CEM细胞凋亡与Bax、Bcl-2、Bcl-XL和caspase 1（ICE）表达增强有关。与未感染对照组相比，HIV感染者的CD 4细胞中Bcl-2和caspase 1的表达增加，而细胞周期蛋白依赖性激酶抑制剂p21 CIP 1的表达减少。HIV感染者的CD 8细胞表现出Bcl-2，Bcl-XL，Bax和caspase 1的表达增加，但在相反的CD 4亚群，他们表现出p21 CIP 1和p16 INK 4a的表达升高与controls.Conclusions：Bax的增加CEM细胞似乎是一个直接的影响与高频率的感染和凋亡，因为它没有被发现在患者的CD 4细胞。相反，患者CD 8细胞中Bax的增加似乎是间接效应。HIV感染的CEM细胞中Bcl-2、Bcl-XL和caspase 1的增加可能是由直接和间接机制引起的，因为它们也发生在HIV感染个体的CD 4和CD 8细胞中。此外，HIV感染者的CD 4亚群中p21 CIP 1的低表达可促进细胞凋亡，而CD 8亚群中p21 CIP 1和p16 INK 4a的高表达可导致无反应性状态，类似于复制性衰老。

Objective:To clarify the molecular mechanisms of HIV-induced apoptosis.Design:The assessment of expression patterns for genes affecting the interrelated cell cycle and apoptosis processes in HIV-1LAI-infected T lymph oblastoid (CEM) cells, as well as CD4 and CD8 cells from HIV-infected individuals and controls.Methods:The kinetics of HIV infection in CEM cells were defined by flow cytometry of green fluorescent protein expression from a reporter vector. Apoptosis of CEM cells was measured by propidium iodine staining and flow cytometry. Gene expression levels were determined by a multiprobe RNase protection assay.Results:The infection and apoptosis of CEM cells were associated with enhanced expression of Bax, Bcl-2, Bcl-X L and caspase 1 (ICE). There was increased expression of Bcl-2 and caspase 1 and decreased expression of cyclin-dependent kinase inhibitor p21 CIP1 in CD4 cells of HIV-infected individuals compared with uninfected controls. The CD8 cells of HIV-infected individuals exhibited increased expression of Bcl-2, Bcl-X L, Bax and caspase 1 but, in contrast to the CD4 subset, they showed elevated expression of p21 CIP1 and p16 INK4a compared with controls.Conclusions:The Bax increase in CEM cells appears to be a direct effect associated with a high frequency of infection and apoptosis, because it was not found in the CD4 cells of patients. In contrast, the increase of Bax in the CD8 cells of patients seems to be an indirect effect. Increases in Bcl-2, Bcl-X L and caspase 1 in HIV-infected CEM cells may be caused by both direct and indirect mechanisms, because they also occurred in CD4 and CD8 cells of HIV-infected individuals. In addition, the low expression of p21 CIP1 in the CD4 subset of HIV-infected individuals could promote apoptosis, whereas the high expression of p21 CIP1 and p16 INK4a in the CD8 subset may lead to a state of anergy, akin to replicative senescence.