Calcium signals and calpain-dependent necrosis are essential for release of coxsackievirus B from polarized intestinal epithelial cells.
Calcium signals and calpain-dependent necrosis are essential for release of coxsackievirus B from polarized intestinal epithelial cells.
复制标题
DOI：
10.1091/mbc.e11-02-0094
复制
发表时间：
2011-09
影响因子：
3.3
通讯作者：
Coyne CB
中科院分区：
文献类型：
--
作者：
Bozym RA;Patel K;White C;Cheung KH;Bergelson JM;Morosky SA;Coyne CB
与非极化细胞相比，柯萨奇病毒B （CVB）感染的极化肠Caco-2细胞发生由肌醇1,4,5-三磷酸受体依赖性钙释放引发的坏死细胞死亡。这种cvb诱导的坏死依赖于Ca2+激活的calpain-2，这是破坏顶端紧密连接复合体所必需的。柯萨奇病毒B （CVB）是肠道病毒家族的一员，在感染早期以肠道上皮细胞极化为靶点。尽管极化上皮具有保护屏障的功能，但CVB可能利用这一屏障促进病毒进入和随后的退出。本研究表明，与非极化细胞相比，cbc感染的极化肠Caco-2细胞发生由肌醇1,4,5-三磷酸受体依赖性钙释放引发的非凋亡性坏死细胞死亡。我们进一步表明，cvb诱导的细胞坏死依赖于Ca2+激活的蛋白酶calpain-2，该蛋白酶参与了cvb诱导的连接复合物的破坏和肌动蛋白细胞骨架的重排。我们的研究阐明了CVB和其他病毒病原体劫持的细胞信号通路，以促进它们在极化细胞类型中的复制和传播。
In contrast to nonpolarized cells, coxsackievirus B (CVB)–infected polarized intestinal Caco-2 cells undergo necrotic cell death triggered by inositol 1,4,5-trisphosphate receptor–dependent calcium release. This CVB-induced necrosis depends on Ca2+-activated calpain-2, which is required for disruption of the apical tight junction complex. Coxsackievirus B (CVB), a member of the enterovirus family, targets the polarized epithelial cells lining the intestinal tract early in infection. Although the polarized epithelium functions as a protective barrier, this barrier is likely exploited by CVB to promote viral entry and subsequent egress. Here we show that, in contrast to nonpolarized cells, CVB-infected polarized intestinal Caco-2 cells undergo nonapoptotic necrotic cell death triggered by inositol 1,4,5-trisphosphate receptor–dependent calcium release. We further show that CVB-induced cellular necrosis depends on the Ca2+-activated protease calpain-2 and that this protease is involved in CVB-induced disruption of the junctional complex and rearrangements of the actin cytoskeleton. Our study illustrates the cell signaling pathways hijacked by CVB, and perhaps other viral pathogens, to promote their replication and spread in polarized cell types.