Garoff H, Hewson R, Opstelten D J
Department of Biosciences at Novum, S-141 57 Huddinge, Sweden.
Microbiol Mol Biol Rev. 1998 Dec;62(4):1171-90. doi: 10.1128/MMBR.62.4.1171-1190.1998.
Enveloped viruses mature by budding at cellular membranes. It has been generally thought that this process is driven by interactions between the viral transmembrane proteins and the internal virion components (core, capsid, or nucleocapsid). This model was particularly applicable to alphaviruses, which require both spike proteins and a nucleocapsid for budding. However, genetic studies have clearly shown that the retrovirus core protein, i.e., the Gag protein, is able to form enveloped particles by itself. Also, budding of negative-strand RNA viruses (rhabdoviruses, orthomyxoviruses, and paramyxoviruses) seems to be accomplished mainly by internal components, most probably the matrix protein, since the spike proteins are not absolutely required for budding of these viruses either. In contrast, budding of coronavirus particles can occur in the absence of the nucleocapsid and appears to require two membrane proteins only. Biochemical and structural data suggest that the proteins, which play a key role in budding, drive this process by forming a three-dimensional (cage-like) protein lattice at the surface of or within the membrane. Similarly, recent electron microscopic studies revealed that the alphavirus spike proteins are also engaged in extensive lateral interactions, forming a dense protein shell at the outer surface of the viral envelope. On the basis of these data, we propose that the budding of enveloped viruses in general is governed by lateral interactions between peripheral or integral membrane proteins. This new concept also provides answers to the question of how viral and cellular membrane proteins are sorted during budding. In addition, it has implications for the mechanism by which the virion is uncoated during virus entry.
包膜病毒通过在细胞膜上出芽而成熟。人们普遍认为，这一过程是由病毒跨膜蛋白与病毒内部成分（核心、衣壳或核衣壳）之间的相互作用驱动的。该模型特别适用于甲病毒，甲病毒出芽需要刺突蛋白和核衣壳两者。然而，遗传学研究清楚地表明，逆转录病毒核心蛋白，即 gag 蛋白，能够自行形成包膜颗粒。此外，负链 RNA 病毒（弹状病毒、正粘病毒和副粘病毒）的出芽似乎主要由内部成分完成，很可能是基质蛋白，因为这些病毒出芽也并非绝对需要刺突蛋白。相比之下，冠状病毒颗粒在没有核衣壳的情况下也能出芽，而且似乎只需要两种膜蛋白。生化和结构数据表明，在出芽过程中起关键作用的蛋白质通过在膜表面或膜内形成三维（笼状）蛋白质晶格来驱动这一过程。同样，最近的电子显微镜研究表明，甲病毒刺突蛋白也参与广泛的侧向相互作用，在病毒包膜外表面形成致密的蛋白质外壳。基于这些数据，我们提出，一般来说，包膜病毒的出芽是由外周或整合膜蛋白之间的侧向相互作用控制的。这一新概念也为病毒出芽过程中病毒和细胞膜蛋白如何分选的问题提供了答案。此外，它对病毒进入过程中病毒粒子脱壳的机制也有影响。
