Coyne Carolyn B, Bergelson Jeffrey M
Division of Infectious Diseases, The Children's Hospital of Philadelphia, University of Pennsylvania, PA 19104, USA.
Cell. 2006 Jan 13;124(1):119-31. doi: 10.1016/j.cell.2005.10.035.
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.
B组柯萨奇病毒（CVB）在引发感染时必须穿过上皮细胞，但发生这种情况的机制仍不确定。柯萨奇病毒和腺病毒受体（CAR）是紧密连接的一个组成部分，从顶端表面接近的病毒无法接触到它。许多CVB还与糖基磷脂酰肌醇锚定蛋白衰变加速因子（DAF）相互作用。在此，我们报告病毒附着在顶端细胞表面的DAF上会激活Abl激酶，触发依赖Rac的肌动蛋白重排，从而使病毒能够移动到紧密连接。在连接处，与CAR的相互作用会促进病毒衣壳的构象变化，这对病毒进入和病毒RNA的释放至关重要。与DAF的相互作用还会激活Fyn激酶，这是小窝蛋白磷酸化以及病毒通过小窝小泡进入细胞所必需的事件。因此，CVB利用DAF介导的信号通路来跨越上皮屏障。
