Posttranslational modification of α-dystroglycan, the cellular receptor for arenaviruses, by the glycosyltransferase LARGE is critical for virus binding
Posttranslational modification of α-dystroglycan, the cellular receptor for arenaviruses, by the glycosyltransferase LARGE is critical for virus binding
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DOI：
10.1128/jvi.79.22.14282-14296.2005
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发表时间：
2005-11-01
影响因子：
5.4
通讯作者：
Oldstone, MBA
中科院分区：
文献类型：
--
作者：
Kunz, S;Rojek, JM;Oldstone, MBA
淋巴细胞性脉络丛脑膜炎病毒（LCMV）、人致病性拉沙热病毒（LFV）和C支新世界沙粒病毒的受体是et-三磷酸甘聚糖（α - dg），一种细胞外基质（ECM）蛋白的细胞表面受体。糖基转移酶LARGE对α - dg的特异性翻译后修饰对于其作为ECM受体的功能至关重要。在目前的研究中，我们发现large依赖性修饰对于α - dg作为沙粒病毒的细胞受体的功能也是至关重要的。病毒结合涉及α - dg的粘蛋白型结构域，并依赖于LARGE的修饰。在LCMV、LFV和沙粒病毒Mobala和Oliveros分离株中，α - dg的大依赖糖基化在病毒结合中起着至关重要的作用。由于LARGE的翻译后修饰对于沙粒病毒和宿主源性配体层粘连蛋白识别α - dg至关重要，因此它也影响病毒和层粘连蛋白对α - dg的竞争。因此，a-DG的大依赖糖基化对病毒-宿主细胞相互作用和人类LFV的发病机制具有重要意义。
The receptor for lymphocytic choriomeningitis virus (LCMV), the human pathogenic Lassa fever virus (LFV), and clade C New World arenaviruses is et-dystroglycan (alpha-DG), a cell surface receptor for proteins of the extracellular matrix (ECM). Specific posttranslational modification of alpha-DG by the glycosyltransferase LARGE is critical for its function as an ECM receptor. In the present study, we show that LARGE-dependent modification is also crucial for alpha-DG's function as a cellular receptor for arenaviruses. Virus binding involves the mucin-type domain of alpha-DG and depends on modification by LARGE. A crucial role of the LARGE-dependent glycosylation of alpha-DG for virus binding is found for several isolates of LCMV, LFV, and the arenaviruses Mobala and Oliveros. Since the posttranslational modification by LARGE is crucial for alpha-DG recognition by both arenaviruses and the host-derived ligand laminin, it also influences competition between virus and laminin for a-DG. Hence, LARGE-dependent glycosylation of a-DG has important implications for the virus-host cell interaction and the pathogenesis of LFV in humans.