Early apoptosis-related changes triggered by HSV-1 in individual neuronlike cells
Early apoptosis-related changes triggered by HSV-1 in individual neuronlike cells
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DOI：
10.1016/s0014-4827(03)00258-1
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发表时间：
2003-09-10
影响因子：
3.7
通讯作者：
Durieux, C
中科院分区：
文献类型：
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作者：
Gautier, I;Coppey, J;Durieux, C
使用强化荧光数字成像显微镜在单细胞水平上研究HSV-1感染后的早期凋亡事件。研究结果表明，分化的ND7神经元样细胞被HSV-1感染后，可触发与细胞凋亡早期阶段相关的生理变化。在感染HSV-1 （KOS菌株）或K26GFP （GFP与HSV-1衣壳蛋白VP26融合）后不到1小时，我们观察到(i)线粒体膜电位中度下降（约20%），（ii）磷脂酰丝氨酸暴露，（iii）线粒体形态改变，由丝状变为球形，（iv） caspase-8激活。在3小时内，这些变化恢复正常，这表明HSV-1感染后细胞凋亡很早就被抵消了。KOS-TK(27)GFP缺乏TK和UL24蛋白，结果相似，提示TK和UL24在细胞凋亡中没有作用。在Vero细胞中，HSV-1感染后未观察到线粒体凋亡过程的特征变化。经uv灭活的K26GFP具有诱导神经元样细胞凋亡的能力。这种实时多参数分析，结合相关的病毒突变体，可能是一种有用的方法来剖析各种病毒基因在感染过程中调节凋亡途径中的作用。(C) 2003 Elsevier Science（美国）版权所有。
Early events of apoptosis following HSV-1 infection were investigated at the single-cell level using intensified fluorescence digital-imaging microscopy. The results provide evidence that infection of differentiated ND7 neuronlike cells by HSV-1 triggers detectable alterations indicative of physiological changes associated with the early stages of apoptosis. Less than 1 h after infection with HSV-1 (KOS strain) or K26GFP (GFP being fused to HSV-1 capsid protein VP26) we observed (i) moderate decrease in mitochondrial membrane potential (about 20%), (ii) exposure of phosphatidyl serine, (iii) morphological change in the mitochondria that became spherical instead of filamentous, and (iv) activation of caspase-8. Within 3 h changes reverted to normal, which indicated that apoptosis was counteracted very early following HSV-1 infection. Similar results were obtained with KOS-TK(27)GFP, lacking TK and UL24 proteins, suggesting that TK and UL24 play no role in apoptosis. In Vero cells mitochondrial changes characteristic of the apoptotic process were not observed following HSV-1 infection. The UV-inactivated K26GFP had the capacity to induce apoptosis in neuronlike cells. This real-time multiparametric analysis, in combination with relevant viral mutants, could be a useful approach for dissecting the roles of various viral genes in modulating apoptotic pathways during infection. (C) 2003 Elsevier Science (USA). All rights reserved.