Kunz Stefan, Campbell Kevin P, Oldstone Michael B A
The Scripps Research Institute, Department of Neuropharmacology, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA.
Virology. 2003 Nov 25;316(2):213-20. doi: 10.1016/j.virol.2003.07.002.
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 alpha-DG functions primarily in the attachment of arenaviruses to the cell surface.
肌营养不良聚糖（DG）是一种高度多功能的细胞表面分子，它在细胞外基质（ECM）和基于肌动蛋白的细胞骨架之间提供分子连接。由单个基因编码，DG经过翻译后加工形成α-DG，一种被鉴定为淋巴细胞性脉络丛脑膜炎病毒（LCMV）和拉沙热病毒（LFV）细胞受体的外周蛋白，以及跨膜亚基β-DG。β-DG与基于肌动蛋白的细胞骨架的连接及其与细胞信号转导网络的关联表明，它可能作为α-DG作为病毒受体活性的必需辅助因子发挥作用。为了解决这个问题，我们构建了一个缺失β-DG胞质结构域的缺失突变体以及α-DG与血小板衍生生长因子受体跨膜结构域的C端融合体。这两个突变体都作为病毒受体发挥功能，表明β-DG在沙粒病毒结合和进入过程中不与α-DG作为辅助因子起作用。这些观察结果与LCMV感染独立于基于肌动蛋白的细胞骨架的结构完整性这一事实一致，并表明α-DG主要在沙粒病毒与细胞表面的附着中起作用。
