Characterization of Marburg virus glycoprotein in viral entry
Characterization of Marburg virus glycoprotein in viral entry
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DOI：
10.1016/j.virol.2006.06.041
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发表时间：
2007-02-05
期刊：
影响因子：
3.7
通讯作者：
Rong, Lijun
中科院分区：
文献类型：
--
作者：
Manicassamy, Balaji;Wang, Jizhen;Rong, Lijun
丝状病毒的宿主嗜性的一个主要决定因素是病毒糖蛋白（GP），其参与受体结合和病毒进入。与埃博拉GP（EGP）相比，马尔堡GP（MGP）在病毒进入方面的特征较差。在这项研究中，使用基于人类免疫缺陷病毒的假型病毒作为替代系统，我们的特点是MGP在病毒进入的作用。我们已经表明，像EGP一样，MGP的粘蛋白样区域（289-501）对于病毒进入不是必需的。我们已经开发了一种针对丝状病毒的病毒进入干扰试验，并且使用该试验，我们已经证明了在靶细胞中转染EGP或MGP可以以剂量依赖性方式干扰EGP/HIV和MGP/HIV假型病毒进入。这些结果与埃博拉病毒和马尔堡病毒使用相同或相关的宿主分子进行病毒进入的观点一致。MGP 1中的非保守残基的取代不损害MGP介导的病毒进入。与EGP 1不同的是，MGP I的许多保守残基的个别取代在MGP表达、掺入HIV病毒体以及因此其介导病毒进入的能力方面产生严重缺陷。这些结果表明，MGP是更敏感的保守残基的取代，这表明MGP可能折叠不同于EGP。(c)2006爱思唯尔公司All rights reserved.
One major determinant of host tropism for filoviruses is viral glycoprotein (GP), which is involved in receptor binding and viral entry. Compared to Ebola GP (EGP), Marburg GP (MGP) is less well characterized in viral entry. In this study, using a human immunodeficiency virus-based pseudotyped virus as a surrogate system, we have characterized the role of MGP in viral entry. We have shown that like EGP, the mucin-like region of MGP (289-501) is not essential for virus entry. We have developed a viral entry interference assay for filoviruses, and using this assay, we have demonstrated that transfection of EGP or MGP in target cells can interfere with EGP/HIV and MGP/HIV pseudotyped virus entry in a dose-dependent manner. These results are consistent with the notion that Ebola and Marburg viruses use the same or a related host molecule(s) for viral entry. Substitutions of the non-conserved residues in MGP1 did not impair MGP-mediated viral entry. Unlike that of EGP1, individual substitutions of many conserved residues of MGP I exerted severe defects in MGP expression, incorporation to HIV virions, and thus its ability to mediate viral entry. These results indicate that MGP is more sensitive to substitutions of the conserved residues, suggesting that MGP may fold differently from EGP. (c) 2006 Elsevier Inc. All rights reserved.