Integrin αvβ3 mediates rotavirus cell entry
Integrin αvβ3 mediates rotavirus cell entry
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DOI：
10.1073/pnas.250299897
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发表时间：
2000-12-19
影响因子：
11.1
通讯作者：
Arias, CF
中科院分区：
文献类型：
--
作者：
Guerrero, CA;Méndez, E;Arias, CF
轮状病毒株的不同之处在于它们需要唾液酸（SA）来与细胞表面进行初始结合；然而，有人提出存在大多数（如果不是全部）轮状病毒株所共有的贴壁后细胞受体。在本研究中，针对α(v)和β(3)整合素亚基以及α(v)β(3)配体玻连蛋白的抗体可有效阻断SA依赖性恒河猴轮状病毒RRV、其SA不依赖性变体nar3和神经氨酸酶抗性人轮状病毒株Wa的感染性。然而，玻连蛋白和抗 β (3) 抗体不会阻止病毒与细胞的结合，表明轮状病毒在结合后步骤（可能是渗透）与 α (v)β (3) 相互作用。这种相互作用被证明与该整联蛋白天然配体中存在的三肽基序精氨酸-甘氨酸-天冬氨酸无关。用 alpha (v)beta (3) 基因转染 CHO 细胞显着增加了它们对所有三种轮状病毒株的许可性，并且通过将这些细胞与 beta (3) 抗体或玻连蛋白一起孵育，可以恢复病毒感染性的增加。这些发现表明α(v)β(3)整合素是神经氨酸酶敏感和神经氨酸酶抗性轮状病毒常见的细胞受体，并支持这种整合素可以至少部分决定细胞对轮状病毒的易感性的假设。
Rotavirus strains differ in their need for sialic acid (SA) for initial binding to the cell surface; however, the existence of a postattachment cell receptor, common to most, if not all, rotavirus strains, has been proposed. In the present study, antibodies to the alpha (v) and beta (3) integrin subunits, and the alpha (v)beta (3) ligand, vitronectin, efficiently blocked the infectivity of the SA-dependent rhesus rotavirus RRV, its SA-independent variant nar3, and the neuraminidase-resistant human rotavirus strain Wa. Vitronectin and anti-beta (3) antibodies, however, did not block the binding of virus to cells, indicating that rotaviruses interact with alpha (v)beta (3) at a postbinding step, probably penetration. This interaction was shown to he independent of the tripeptide motif arginine-glycine-aspartic acid present in the natural ligands of this integrin. Transfection of CHO cells with alpha (v)beta (3) genes significantly increased their permissiveness to all three rotavirus strains, and the increment of virus infectivity was reverted by incubation of these cells either with antibodies to beta (3) or with vitronectin. These findings implicate alpha (v)beta (3) integrin as a cellular receptor common to neuraminidase-sensitive and neuraminidase-resistant rotaviruses, and support the hypothesis that this integrin could determine, at least in part, the cellular susceptibility to rotaviruses.