α-dystroglycan can mediate arenavirus infection in the absence of β-dystroglycan
α-dystroglycan can mediate arenavirus infection in the absence of β-dystroglycan
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DOI：
10.1016/j.virol.2003.07.002
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发表时间：
2003-11-25
期刊：
影响因子：
3.7
通讯作者：
Oldstone, MBA
中科院分区：
文献类型：
--
作者：
Kunz, S;Campbell, KP;Oldstone, MBA
营养不良多糖(DG)是一种高度多功能的细胞表面分子，在细胞外基质(ECM)和基于肌动蛋白的细胞骨架之间提供分子联系。DG由单个基因编码，翻译后加工形成α-DG，这是一种外周蛋白，被认为是淋巴细胞性脉络膜脑膜炎病毒(LCMV)和拉沙热病毒(LFV)的细胞受体，以及跨膜亚单位β-DG。β-DG与以肌动蛋白为基础的细胞骨架的联系及其与细胞信号转导网络的联系表明，它可能是α-DG作为病毒受体的活性的重要辅助因子。为了解决这个问题，我们构建了一个缺失β-DG胞浆结构域的缺失突变体，并在α-DG和PDGF受体的跨膜结构域之间进行了C端融合。这两个突变体都具有病毒受体的功能，表明β-DG与α-DG不是Arena病毒结合和进入的辅助因子。这些观察结果与LCMV感染独立于以肌动蛋白为基础的细胞骨架的结构完整性这一事实相一致，并表明a-DG主要在ArenaVirus与细胞表面的附着中发挥作用。(C)2003 Elsevier Inc.保留所有权利。
Dystroglycan (DG) is a highly versatile cell surface molecule that provides a molecular link between the extracellular matrix (ECM) and the actin-based cytoskeleton. Encoded by a single gene, DG is posttranslationally processed to form alpha-DG, a peripheral protein identified as the cellular receptor for lymphocytic choriomeningitis virus (LCMV) and Lassa fever virus (LFV), and the membrane-spanning subunit beta-DG. The link of beta-DG to the actin-based cytoskeleton and its association with the cellular signal transduction network suggest that it may function as an essential cofactor for the activity of alpha-DG as a virus receptor. To address this issue, we constructed a deletion mutant lacking the cytoplasmic domain of beta-DG and a C-terminal fusion between alpha-DG and the transmembrane domain of PDGF receptor. Both mutants were functional as virus receptors, indicating that beta-DG does not act as a cofactor with alpha-DG for arenavirus binding and entry. These observations are in agreement with the fact that LCMV infection is independent from the structural integrity of the actin-based cytoskeleton and suggest that a-DG functions primarily in the attachment of arenaviruses to the cell surface. (C) 2003 Elsevier Inc. All rights reserved.