Wieringa Roeland, de Vries Antoine A F, van der Meulen Jannes, Godeke Gert-Jan, Onderwater Jos J M, van Tol Hans, Koerten Henk K, Mommaas A Mieke, Snijder Eric J, Rottier Peter J M
Virology Division, Department of Infectious Diseases and Immunology, Yalelaan 1, 3584 CL Utrecht, The Netherlands.
J Virol. 2004 Dec;78(23):13019-27. doi: 10.1128/JVI.78.23.13019-13027.2004.
Equine arteritis virus (EAV) is an enveloped, positive-stranded RNA virus belonging to the family Arteriviridae of the order Nidovirales. EAV particles contain seven structural proteins: the nucleocapsid protein N, the unglycosylated envelope proteins M and E, and the N-glycosylated membrane proteins GP(2b) (previously named G(S)), GP(3), GP(4), and GP(5) (previously named G(L)). Proteins N, M, and GP(5) are major virion components, E occurs in virus particles in intermediate amounts, and GP(4), GP(3), and GP(2b) are minor structural proteins. The M and GP(5) proteins occur in virus particles as disulfide-linked heterodimers while the GP(4), GP(3), and GP(2b) proteins are incorporated into virions as a heterotrimeric complex. Here, we studied the effect on virus assembly of inactivating the structural protein genes one by one in the context of a (full-length) EAV cDNA clone. It appeared that the three major structural proteins are essential for particle formation, while the other four virion proteins are dispensable. When one of the GP(2b), GP(3), or GP(4) proteins was missing, the incorporation of the remaining two minor envelope glycoproteins was completely blocked while that of the E protein was greatly reduced. The absence of E entirely prevented the incorporation of the GP(2b), GP(3), and GP(4) proteins into viral particles. EAV particles lacking GP(2b), GP(3), GP(4), and E did not markedly differ from wild-type virions in buoyant density, major structural protein composition, electron microscopic appearance, and genomic RNA content. On the basis of these results, we propose a model for the EAV particle in which the GP(2b)/GP(3)/GP(4) heterotrimers are positioned, in association with a defined number of E molecules, above the vertices of the putatively icosahedral nucleocapsid.
马动脉炎病毒(EAV)是一种有包膜的正链RNA病毒,属于尼多病毒目动脉炎病毒科。EAV病毒粒子包含七种结构蛋白:核衣壳蛋白N、未糖基化的包膜蛋白M和E,以及N-糖基化的膜蛋白GP(2b)(以前称为G(S))、GP(3)、GP(4)和GP(5)(以前称为G(L))。蛋白N、M和GP(5)是主要的病毒粒子成分,E在病毒粒子中的含量中等,而GP(4)、GP(3)和GP(2b)是次要的结构蛋白。M和GP(5)蛋白以二硫键连接的异二聚体形式存在于病毒粒子中,而GP(4)、GP(3)和GP(2b)蛋白以异三聚体复合物的形式掺入病毒粒子。在此,我们研究了在(全长)EAV cDNA克隆的背景下逐一灭活结构蛋白基因对病毒组装的影响。结果表明,三种主要结构蛋白对于病毒粒子形成至关重要,而其他四种病毒粒子蛋白则是可有可无的。当缺少GP(2b)、GP(3)或GP(4)蛋白之一时,其余两种次要包膜糖蛋白的掺入完全受阻,而E蛋白的掺入则大大减少。E的缺失完全阻止了GP(2b)、GP(3)和GP(4)蛋白掺入病毒粒子。缺乏GP(2b)、GP(3)、GP(4)和E的EAV病毒粒子在浮力密度、主要结构蛋白组成、电子显微镜外观和基因组RNA含量方面与野生型病毒粒子没有明显差异。基于这些结果,我们提出了一个EAV病毒粒子模型,其中GP(2b)/GP(3)/GP(4)异三聚体与一定数量的E分子结合,位于假定的二十面体核衣壳的顶点上方。