Involvement of bovine leukemia virus in induction and inhibition of apoptosis
Involvement of bovine leukemia virus in induction and inhibition of apoptosis
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DOI：
10.1016/j.micinf.2004.09.014
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发表时间：
2005-01-01
影响因子：
5.8
通讯作者：
Aida, Y
中科院分区：
文献类型：
--
作者：
Takahashi, M;Tajima, S;Aida, Y
在以前的研究中，我们确定了牛白血病病毒（BLV）Tax蛋白的一种有趣的突变形式，命名为D247 G。与野生型Tax（wt-Tax）相比，其具有增强的反式激活BLV的长末端重复序列（LTR）和细胞原癌基因c-fos的能力。我们在此证明，含有Tax突变体D247 G形式的BLV感染性菌株在其积极和消极调节细胞存活的能力方面也不同。当感染野生型或突变型BLV的外周血单核细胞（PBMC）与星形孢菌素（一种已知诱导调节细胞凋亡的线粒体半胱天冬酶级联途径的试剂）离体培养时，与野生型BLV相比，感染突变型BLV的细胞中细胞凋亡速率降低的程度更大，这与先前在没有星形孢菌素的培养物中的观察结果一致。存活率的增加与bcl-xl mRNA表达的增加有关，但与离体bcl-2和bax mRNA表达的增加无关。与此相反，当一个组织培养适应细胞系，293 T，瞬时转染野生型或突变BLV，诱导细胞凋亡。细胞凋亡率的增加在转染突变BLV的细胞中更高。在用野生型和突变型D247 G Tax瞬时转染的细胞中注意到相同的差异，表明观察到的细胞存活的正和负调节归因于突变型D247 G Tax的功能特征。(C)2004年，Elsevier SAS。All rights reserved.
In a previous study, we identified an interesting mutant form of the Tax protein of bovine leukemia virus (BLV), designated D247G. that has an enhanced capacity to transactivate the long terminal repeat (LTR) of BLV and the cellular proto-oncogene c-fos when compared with wild-type Tax (wt-Tax). We domonstrate here that an infectious strain of BLV containing the mutant D247G form of Tax also differs in its capacity to modulate cell survival both positively and negatively. When peripheral blood mononuclear cells (PBMCs) infected with wild-type or mutant BLV are cultured ex vivo with staurosporine, an agent known to induce a mitochondrial caspase cascade pathway regulating apoptosis, the rate of apoptosis is reduced to a greater extent in cells infected with mutant BLV than wild-type BLV, consistent with previous observations in cultures without staurosporine. The increase in survival was associated with an increase in expression of mRNA of bcl-xl but not bcl-2 and bax ex vivo. In contrast, when a tissue culture-adapted cell line, 293T, was transiently transfected with either wild-type or mutant BLV, apoptosis was induced. The increase in the rate of apoptosis was higher in cells transfected with mutant BLV. The same difference was noted in cells transiently transfected with wild-type and mutant D247G Tax, suggesting that the observed positive and negative modulation of cell survival is attributed to the functional characteristics of mutant D247G Tax. (C) 2004 Elsevier SAS. All rights reserved.