β1 integrin mediates internalization of mammalian reovirus
β1 integrin mediates internalization of mammalian reovirus
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DOI：
10.1128/jvi.80.6.2760-2770.2006
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发表时间：
2006-03-01
影响因子：
5.4
通讯作者：
Dermody, TS
中科院分区：
文献类型：
--
作者：
Maginnis, MS;Forrest, JC;Dermody, TS
呼肠孤病毒感染是由附着蛋白 sigma 1 与细胞表面碳水化合物和连接粘附分子 A (JAM-A) 之间的相互作用引发的。在不允许的细胞中表达缺乏细胞质尾部的 JAM-A 突变体赋予对呼肠孤病毒感染的完全易感性，这表明除 JAM-A 之外的细胞表面分子在附着后介导病毒内化。呼肠孤病毒外衣壳蛋白 lambda 2（充当 sigma 1 的结构基础）中存在整合素结合序列，表明整合素介导呼肠孤病毒内吞作用。 β1 整合素特异性抗体（但不是其他整合素亚基特异性抗体）抑制了 HeLa 细胞的呼肠孤病毒感染。在不允许的鸡胚成纤维细胞中，β1 整合素 cDNA 以及编码 JAM-A 的 cDNA 的表达赋予了呼肠孤病毒感染的易感性。与表达 PI 的同基因细胞相比，β1 缺陷型小鼠胚胎干细胞中呼肠孤病毒的感染性显着降低。然而，呼肠孤病毒与β1表达水平不同的细胞等价结合，表明β1整合素参与了附着后进入步骤。一致地，与表达β1的细胞中的病毒摄取相比，β1缺陷细胞中呼肠孤病毒病毒体的摄取显着减少。这些数据提供证据表明β1整合素促进呼肠孤病毒内化，并表明病毒进入是通过呼肠孤病毒病毒体与细胞表面上独立的附着和进入受体的相互作用而发生的。
Reovirus infection is initiated by interactions between the attachment protein sigma 1 and cell surface carbohydrate and junctional adhesion molecule A (JAM-A). Expression of a JAM-A mutant lacking a cytoplasmic tail in nonpermissive cells conferred full susceptibility to reovirus infection, suggesting that cell surface molecules other than JAM-A mediate viral internalization following attachment. The presence of integrin-binding sequences in reovirus outer capsid protein lambda 2, which serves as the structural base for sigma 1, suggests that integrins mediate reovirus endocytosis. A beta 1 integrin-specific antibody, but not antibodies specific for other integrin subunits, inhibited reovirus infection of HeLa cells. Expression of a beta 1 integrin cDNA, along with a cDNA encoding JAM-A, in nonpermissive chicken embryo fibroblasts conferred susceptibility to reovirus infection. Infectivity of reovirus was significantly reduced in beta 1-deficient mouse embryonic stem cells in comparison to isogenic cells expressing PI. However, reovirus bound equivalently to cells that differed in levels of beta 1 expression, suggesting that beta 1 integrins are involved in a postattachment entry step. Concordantly, uptake of reovirus virions into beta 1-deficient cells was substantially diminished in comparison to viral uptake into beta 1-expressing cells. These data provide evidence that beta 1 integrin facilitates reovirus internalization and suggest that viral entry occurs by interactions of reovirus virions with independent attachment and entry receptors on the cell surface.