Protease-defective, gp120-containing human immunodeficiency virus type 1 particles induce apoptosis more efficiently than does wild-type virus or recombinant gp120 protein in healthy donor-derived peripheral blood T cells
Protease-defective, gp120-containing human immunodeficiency virus type 1 particles induce apoptosis more efficiently than does wild-type virus or recombinant gp120 protein in healthy donor-derived peripheral blood T cells
复制标题
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：
--
复制
发表时间：
1997
影响因子：
9.4
通讯作者：
Kazuyoshi Ikuta
中科院分区：
文献类型：
--
作者：
Masanori Kameoka;Takuro Kimura;Yong Hui Zheng;Satoko Suzuki;Koh Fujinaga;Ronald B. Luftig;Kazuyoshi Ikuta
细胞凋亡和合胞体形成是人类免疫缺陷病毒1型（HIV-1）损害未感染的CD4 + T细胞功能的两种机制，并且主要参与疾病向AIDS的进展。以前，我们表明，gp120含有，蛋白酶缺陷的HIV-1（L-2）颗粒产生合胞体的颗粒介导的融合与未感染的培养的CD4 + T细胞。在这里，我们提出的证据表明，这样的L-2颗粒可以诱导40至50%的T细胞，这是从HIV-1阴性的健康供体来源的外周血单核细胞（PBMC-Ts）富集的细胞凋亡。与L-2颗粒孵育后，用植物血凝素、伴刀豆球蛋白A或离子霉素激活PBMC-Ts，导致增殖能力丧失，并在3天内逐渐诱导细胞凋亡。野生型菌株LAI颗粒或重组gp120在诱导这种细胞凋亡方面的效率明显较低（<或= 15%）。Western印迹（免疫印迹）分析表明，L-2颗粒含有大量的Env gp120比LAI颗粒。PBMC-T与Fas拮抗剂预孵育或L-2颗粒与可溶性CD 4预孵育均可阻断大部分细胞凋亡。这表明L-2样颗粒在HIV-1诱导的未感染的旁观者细胞凋亡中起重要作用。
Apoptosis and syncytium formation are two mechanisms by which human immunodeficiency virus type 1 (HIV-1) impairs uninfected CD4+ T-cell function and are mainly involved in the progression of the disease to AIDS. Previously, we showed that gp120-containing, protease-deficient HIV-1 (L-2) particles generated syncytia by particle-mediated fusion with uninfected cultured CD4+ T cells. Here, we present evidence that such L-2 particles can induce apoptosis in 40 to 50% of T cells which were enriched from HIV-1-negative healthy donor-derived peripheral blood mononuclear cells (PBMC-Ts). Activation of PBMC-Ts with phytohemagglutinin, concanavalin A, or ionomycin after incubation with L-2 particles resulted in the loss of proliferative capacity and gradual induction of apoptosis over 3 days. Wild-type strain LAI particles or recombinant gp120 were markedly less efficient (< or = 15%) at inducing such apoptosis. Western blot (immunoblot) analysis revealed that L-2 particles contained a larger amount of Env gp120 than LAI particles. Either preincubation of PBMC-Ts with a Fas antagonist or preincubation of L-2 particles with soluble CD4 blocked most of the apoptosis. This suggests that L-2-like particles can play a major role in HIV-1-induced apoptosis of uninfected bystander cells.
影响因子：
20.3
作者：
N. Oyaizu;T. McCloskey;Maria Coronesi;N. Chirmule;V. Kalyanaraman;S. Pahwa
通讯作者：
N. Oyaizu;T. McCloskey;Maria Coronesi;N. Chirmule;V. Kalyanaraman;S. Pahwa
使用 3-磷酸甘油醛脱氢酶作为内部对照，通过竞争性聚合酶链反应对基质 Gla 蛋白 mRNA 进行定量。
影响因子：
3.5
作者：
Zhao,J;Araki,N;Nishimoto,SK
通讯作者：
Nishimoto,SK
影响因子：
56.9
作者：
PIATAK, M;SAAG, MS;LIFSON, JD
通讯作者：
LIFSON, JD