Sialic acid functions in enterovirus 70 binding and infection
Sialic acid functions in enterovirus 70 binding and infection
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DOI：
10.1128/jvi.76.22.11265-11272.2002
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发表时间：
2002-11-01
影响因子：
5.4
通讯作者：
Dimock, K
中科院分区：
文献类型：
--
作者：
Alexander, DA;Dimock, K
病毒与宿主细胞受体的相互作用是病毒感染的第一步，是病毒宿主范围、组织向性和发病机制的重要决定因素。补体调节蛋白衰变加速因子 (DAF/CD55) 是肠道病毒 70 (EV70) 的附着受体，肠道病毒 70 属于小核糖核酸病毒科，通常与人类眼部感染（称为急性出血性结膜炎）相关。在早期研究中，红细胞上负责其血凝活性的 EV70 受体被证明对神经氨酸酶敏感，这意味着唾液酸在病毒附着中发挥着重要作用。在这里，我们扩展了这些结果，表明细胞表面唾液酸是 EV70 与易受病毒感染的有核细胞结合所必需的，并且唾液酸结合在生产性感染中很重要。通过使用定点诱变消除 DAF 和嵌合受体蛋白的单个 N 连接糖基化位点（其中 DAF 的 O 糖基化结构域被 HLA-B44 分子的一个区域取代），排除了 EV70 与 DAF 唾液酸残基结合的作用，表明细胞表面至少存在一种额外的唾液酸化 EV70 结合因子。用糖基化代谢抑制剂处理细胞排除了糖蛋白的 N-连接寡糖的作用，但表明 O-连接糖基化对于 EV70 结合很重要。
The interaction of viruses with host cell receptors is the initial step in viral infection and is an important determinant of virus host range, tissue tropism, and pathogenesis. The complement regulatory protein decay-accelerating factor (DAF/CD55) is an attachment receptor for enterovirus 70 (EV70), a member of the Picornaviridae, commonly associated with an eye infection in humans known as acute hemorrhagic conjunctivitis. In early work, the EV70 receptor on erythrocytes, responsible for its hemagglutinating activity, was shown to be sensitive to neuraminidase, implying an essential role for sialic acid in virus attachment. Here, we extend these results to show that cell surface sialic acid is required for EV70 binding to nucleated cells susceptible to virus infection and that sialic acid binding is important in productive infection. Through the use of site-directed mutagenesis to eliminate the single N-linked glycosylation site of DAF and of a chimeric receptor protein in which the O-glycosylated domain of DAF was replaced by a region of the HLA-B44 molecule, a role in EV70 binding for the sialic acid residues of DAF was excluded, suggesting the existence of at least one additional, sialylated EV70-binding factor at the cell surface. Treatment of cells with metabolic inhibitors of glycosylation excluded a role for the N-linked oligosaccharides of glycoproteins but suggested that O-linked glycosylation is important for EV70 binding.