O mannosylation of α-dystroglycan is essential for lymphocytic choriomeningitis virus receptor function
O mannosylation of α-dystroglycan is essential for lymphocytic choriomeningitis virus receptor function
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DOI：
10.1128/jvi.79.22.14297-14308.2005
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发表时间：
2005-11-01
影响因子：
5.4
通讯作者：
Oxenius, A
中科院分区：
文献类型：
--
作者：
Imperiali, M;Thoma, C;Oxenius, A
α-肌营养不良聚糖（α-DG）被鉴定为淋巴细胞性脉络丛脑膜炎病毒（LCMW）和包括人致病性拉沙热病毒的几种其它沙粒病毒的共同受体。最初的工作假设沙粒病毒糖蛋白和α-DG之间的相互作用是基于蛋白质-蛋白质相互作用。然而，我们发现，对LCMV感染的易感性不同的细胞系，尽管他们表达相当水平的DG，这表明α-DG的翻译后修饰将参与病毒受体功能。在这里，我们证明了α-DG的糖基化，特别是0甘露糖基化，这是一种罕见的O-连接的糖基化在哺乳动物中，是必不可少的LCMV受体功能。O-甘露糖基化途径组分缺陷的细胞显示出显著降低的LCMV感染性。由于缺陷性O甘露糖基化与哺乳动物的严重临床症状（如先天性肌营养不良症）相关，因此LCMV和潜在的其他沙粒病毒可能选择这种保守且关键的翻译后修饰作为细胞进入和感染的主要靶结构。
alpha-Dystroglycan (alpha-DG) was identified as a common receptor for lymphocytic choriomeningitis virus (LCMW) and several other arenaviruses including the human pathogenic Lassa fever virus. Initial work postulated that interactions between arenavirus glycoproteins and alpha-DG are based on protein-protein interactions. We found, however, that susceptibility toward LCMV infection differed in various cell lines despite them expressing comparable levels of DG, suggesting that posttranslational modifications of alpha-DG would be involved in viral receptor function. Here, we demonstrate that glycosylation of alpha-DG, and in particular, 0 mannosylation, which is a rare type of O-linked glycosylation in mammals, is essential for LCMV receptor function. Cells that are defective in components of the O-mannosylation pathway showed strikingly reduced LCMV infectibility. As defective O mannosylation is associated with severe clinical symptoms in mammals such as congenital muscular dystrophies, it is likely that LCMV and potentially other arenaviruses may have selected this conserved and crucial posttranslational modification as the primary target structure for cell entry and infection.