Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 35294.
Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14850; email:
Annu Rev Virol. 2014 Nov;1(1):561-80. doi: 10.1146/annurev-virology-031413-085427. Epub 2014 Jul 3.
Assembly, part of the late stages of the retroviral life cycle, begins when the structural polyprotein Gag associates with viral genomic RNA. Ultimately, more than a thousand Gag molecules form a spherical immature virion. Maturation takes place soon after or concomitantly with virus budding and is initiated as Gag is cleaved by the retroviral protease into its constituent protein domains. The immature core is thought to disassemble and the liberated CA proteins to reassemble into a morphologically distinct mature capsid. In vitro assembly with derivatives of Gag and CA has been used to study retroviruses for over two decades. In this review, we examine the discovery and development of three major model systems [human immunodeficiency virus type 1 (HIV-1), Rous sarcoma virus (RSV), and Mason-Pfizer monkey virus (MPMV)] and discuss structural features and aspects of the retroviral assembly pathway that have been uncovered using in vitro assembly. We also put forward two major unresolved questions in the field and propose future avenues of research.
装配是逆转录病毒生命周期的晚期阶段之一,当结构蛋白多聚 Gag 与病毒基因组 RNA 结合时开始。最终,一千多个 Gag 分子形成一个球形的不成熟病毒粒子。成熟发生在病毒芽出后不久或同时进行,并且随着逆转录病毒蛋白酶将 Gag 切割成其组成的蛋白结构域而开始。不成熟的核心被认为会解体,而游离的 CA 蛋白会重新组装成形态上不同的成熟衣壳。用 Gag 和 CA 的衍生物进行体外装配已经用于研究逆转录病毒超过二十年。在这篇综述中,我们检查了三个主要模型系统(人类免疫缺陷病毒 1 (HIV-1)、 Rous 肉瘤病毒 (RSV) 和 Mason-Pfizer 猴病毒 (MPMV))的发现和发展,并讨论了使用体外装配揭示的逆转录病毒装配途径的结构特征和方面。我们还提出了该领域的两个主要未解决的问题,并提出了未来的研究方向。