Ability to induce p53 and caspase-mediated apoptosis in primary CD4+ T cells is variable among primary isolates of human immunodeficiency virus type 1.

Ability to induce p53 and caspase-mediated apoptosis in primary CD4+ T cells is variable among primary isolates of human immunodeficiency virus type 1.
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在 1 型人类免疫缺陷病毒的初级分离株中,诱导原代 CD4 T 细胞中 p53 和 caspase 介导的细胞凋亡的能力各不相同。

DOI:
10.1089/088922202753614209
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发表时间:
2002
影响因子:
1.5
通讯作者:
K. Ikuta
K. Ikuta
中科院分区:
医学4区
文献类型:
--
作者:
S. Komoto;M. Kinomoto;H. Horikoshi;Miki Shiraga;T. Kurosu;T. Mukai;W. Auwanit;T. Otake;I. Oishi;K. Ikuta

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人类免疫缺陷病毒1型(HIV-1)感染与CD 4(+)T细胞的急剧耗竭有关,这是HIV-1诱导的主要发病机制。细胞凋亡在T细胞耗竭中起重要作用,并提出了许多T细胞凋亡的机制。在这里,我们比较了几种实验室毒株和HIV-1亚型B和E的原代分离株在原代外周血单个核细胞(PBMC)中诱导凋亡的水平。结果表明,受感染的PBMC中的细胞凋亡,优先在CD 4 + T细胞群体中,通过流式细胞术末端转移酶dUTP缺口末端标记(TUNEL)技术和核染料Hoechst 33342染色在病毒产生的时间附近变得可检测。在单个分离株中诱导PBMC凋亡的能力是高度可变的。p53蛋白在感染的PBMC中的表达在病毒产生之前就开始增加,并且p53蛋白的水平几乎与分离株诱导的凋亡率成正比。在Z-VAD-FMK存在下感染和培养的细胞具有显著降低的细胞死亡率,表明活化的半胱天冬酶在凋亡中也起重要作用。因此,HIV-1诱导的原代T细胞凋亡伴随着原代分离株中不同水平的p53蛋白和半胱天冬酶激活。
Infection with human immunodeficiency virus type 1 (HIV-1) is associated with dramatic depletion of CD4(+) T cells, the major HIV-1-induced pathogenesis. Apoptosis has been suggested to play an important role for the T cell depletion and a number of mechanisms have been proposed for the apoptosis in T cells. Here, we compared the levels for apoptosis induction in primary peripheral blood mononuclear cells (PBMCs) among several laboratory strains and primary isolates of the HIV-1 subtypes B and E. The results showed that apoptosis in infected PBMCs, preferentially in CD4+ T cell population, became detectable around the time for virus production by flow cytometric terminal transferase dUTP nick end labeling (TUNEL) technique and staining with the nuclear dye Hoechst 33342. The abilities to induce apoptosis in PBMCs were highly variable in individual isolates. The increase of p53 protein in infected PBMCs, which was initiated before virus production, was observed in infected PBMCs and the levels of p53 protein were almost proportional to the rates of the isolates to induced apoptosis. The cells infected and cultured in the presence of Z-VAD-FMK had significantly decreased cell mortalities, indicating that activated caspases also played a significant role in the apoptosis. Thus, HIV-1-induced apoptosis in primary T cells was accompanied by the p53 protein and caspase activation at varied levels in primary isolates.
Estaquier, J.:“Fas 介导的人类免疫缺陷病毒感染者的 CD4 和 CD8 T 细胞凋亡:细胞因子和蛋白酶拮抗剂的不同体外预防作用”血液。
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DOI: 10.1038/35071111
发表时间: 2001-04-12
期刊: NATURE
影响因子: 64.8
作者:
Geleziunas, R;Xu, WD;Greene, WC
通讯作者: Greene, WC
在健康供体来源的外周血 T 细胞中,蛋白酶缺陷型、含有 gp120 的人类免疫缺陷病毒 1 型颗粒比野生型病毒或重组 gp120 蛋白更有效地诱导细胞凋亡
DOI: --
发表时间: 1997
影响因子: 9.4
作者:
Masanori Kameoka;Takuro Kimura;Yong Hui Zheng;Satoko Suzuki;Koh Fujinaga;Ronald B. Luftig;Kazuyoshi Ikuta
通讯作者: Kazuyoshi Ikuta