Viroporins from RNA viruses induce caspase-dependent apoptosis
Viroporins from RNA viruses induce caspase-dependent apoptosis
复制标题
DOI：
10.1111/j.1462-5822.2007.01057.x
复制
发表时间：
2008-02-01
影响因子：
3.4
通讯作者：
Carrasco, Luis
中科院分区：
文献类型：
--
作者：
Madan, Vanessa;Castello, Alfredo;Carrasco, Luis
已知病毒编码的病毒素可以改变细胞膜的通透性，并在病毒萌发过程中发挥重要作用。在这里，比较分析了几种病毒孔蛋白在幼年仓鼠肾细胞中的膜通透性。Sindbis病毒的6K蛋白、小鼠肝炎病毒的E蛋白、甲型流感病毒的M2蛋白以及脊髓灰质炎病毒的2B和3A蛋白的合成都不同程度地提高了膜的通透性。我们发现丙型肝炎病毒的两种蛋白，p7和NS4A，也显示出与6K蛋白相当的病毒孢子蛋白活性。除了破坏离子细胞稳态和促进细菌细胞裂解的能力外，表达的病毒孔蛋白还能够诱导细胞死亡。病毒孔蛋白表达可引起核小体间DNA降解和凋亡小体的产生。翻译起始因子4GI和多聚(ADP-核糖)聚合酶的裂解一致表明效应器caspase-3被激活。我们发现脊髓灰质炎病毒2B部分定位于线粒体，并导致这些细胞器在核周围的异常分布。在表达其他病毒素后，线粒体形态也发生了改变。最后，从线粒体释放细胞色素c的检测表明，线粒体途径参与了病毒孢菌素诱导的细胞凋亡。这些发现表明，病毒孔蛋白可诱导caspase依赖的程序性细胞死亡。
The virus-encoded viroporins are known to modify membrane permeability and play an essential role in virus budding. Here, a comparative analysis of the membrane permeabilization capacity of a number of viroporins was performed in baby hamster kidney cells. Synthesis of 6K protein from Sindbis virus, E from mouse hepatitis virus, M2 from influenza A virus, and 2B and 3A from poliovirus enhanced membrane permeability to different extents. We show that two proteins from hepatitis C virus, p7 and NS4A, also display viroporin activity to a level comparable to 6K protein. In addition to their capacity to disrupt ionic cellular homeostasis and promote bacterial cell lysis, the expressed viroporins were able to induce cell death. Degradation of internucleosomal DNA and generation of apoptotic bodies were observed upon viroporin expression. Consistently, cleavage of translation initiation factor 4GI and poly-(ADP-ribose) polymerase indicated activation of effector caspase-3. We found that poliovirus 2B localizes partially in mitochondria and induces an anomalous perinuclear distribution of these organelles. Mitochondria morphology was also altered after expression of other viroporins. Finally, detection of cytochrome c release from mitochondria suggests involvement of the mitochondrial pathway in viroporin-induced apoptosis. These findings suggest that viroporins induce caspase-dependent programmed cell death.