Virus-induced Abl and Fyn kinase signals permit coxsackievirus entry through epithelial tight junctions
Virus-induced Abl and Fyn kinase signals permit coxsackievirus entry through epithelial tight junctions
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DOI：
10.1016/j.cell.2005.10.035
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发表时间：
2006-01-13
期刊：
影响因子：
64.5
通讯作者：
Bergelson, JM
中科院分区：
文献类型：
--
作者：
Coyne, CB;Bergelson, JM
组B柯萨奇病毒（CVB）必须通过上皮细胞，因为他们开始感染，但发生的机制仍然不确定。柯萨奇病毒和腺病毒受体（CAR）是紧密连接的一个组成部分，病毒从顶端表面接近时无法接近。许多CVB也与GPI锚定的蛋白质衰变加速因子（decay-accelerating factor，CVB）相互作用。在这里，我们报告说，病毒附着在顶端细胞表面的细胞膜上激活Abl激酶，触发Rac依赖的肌动蛋白重排，使病毒移动到紧密连接。在接合部内，与CAR的相互作用促进病毒衣壳中的构象变化，这对于病毒进入和病毒RNA的释放是必需的。与β-淀粉样蛋白的相互作用还激活Fyn激酶，这是小窝蛋白磷酸化和病毒在小窝囊泡内转运到细胞中所需的事件。因此，CVB利用DAF介导的信号传导途径来克服上皮屏障。
Group B coxsackieviruses (CVBs) must cross the epithelium as they initiate infection, but the mechanism by which this occurs remains uncertain. The coxsackievirus and adenovirus receptor (CAR) is a component of the tight junction and is inaccessible to virus approaching from the apical surface. Many CVBs also interact with the GPI-anchored protein decay-accelerating factor (DAF). Here, we report that virus attachment to DAF on the apical cell surface activates Abl kinase, triggering Rac-dependent actin rearrangements that permit virus movement to the tight junction. Within the junction, interaction with CAR promotes conformational changes in the virus capsid that are essential for virus entry and release of viral RNA. Interaction with DAF also activates Fyn kinase, an event that is required for the phosphorylation of caveolin and transport of virus into the cell within caveolar vesicles. CVBs thus exploit DAF-mediated signaling pathways to surmount the epithelial barrier.