How HIV-1 Gag assembles in cells: Putting together pieces of the puzzle.
How HIV-1 Gag assembles in cells: Putting together pieces of the puzzle.
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DOI：
10.1016/j.virusres.2014.07.001
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发表时间：
2014-11-26
期刊：
影响因子：
5
通讯作者：
Robinson BA
中科院分区：
文献类型：
--
作者：
Lingappa JR;Reed JC;Tanaka M;Chutiraka K;Robinson BA
在病毒生命周期的后期，HIV-1 Gag组装成一个球形的未成熟衣壳，并经历萌芽、释放和成熟。本文从突变分析、结构研究、纯化的重组GAG的组装、新翻译的GAG在无细胞体系中的组装以及利用生化和成像技术在细胞中的研究等五个不同的角度综述了涉及未成熟衣壳组装的事件。我们总结了使用每种方法获得的关键发现，指出了哪里有共识，并强调了尚未回答的问题。特别强调的是协调数据，表明GAG按照两种不同的路径组装，具体取决于装配环境。具体地说，在缺乏细胞蛋白质的组装系统中，高浓度的GAG可以利用纯化的核酸作为支架自发组装。然而，在更复杂的细胞内环境中，限制自组装的障碍以细胞蛋白质、细胞器、宿主防御和缺乏游离核酸的形式存在。为了克服这些障碍，并在不利的环境中促进有效的未成熟衣壳的形成，GAG似乎利用了细胞中依赖能量的、宿主催化的组装中间产物的途径。总体而言，我们展示了使用各种技术获得的数据如何导致我们目前对艾滋病毒组装的理解。
During the late stage of the viral life cycle, HIV-1 Gag assembles into a spherical immature capsid, and undergoes budding, release, and maturation. Here we review events involved in immature capsid assembly from the perspective of five different approaches used to study this process: mutational analysis, structural studies, assembly of purified recombinant Gag, assembly of newly-translated Gag in a cell-free system, and studies in cells using biochemical and imaging techniques. We summarize key findings obtained using each approach, point out where there is consensus, and highlight unanswered questions. Particular emphasis is placed on reconciling data suggesting that Gag assembles by two different paths, depending on the assembly environment. Specifically, in assembly systems that lack cellular proteins, high concentrations of Gag can spontaneously assemble using purified nucleic acid as a scaffold. However, in the more complex intracellular environment, barriers that limit self-assembly are present in the form of cellular proteins, organelles, host defenses, and the absence of free nucleic acid. To overcome these barriers and promote efficient immature capsid formation in an unfavorable environment, Gag appears to utilize an energy-dependent, host-catalyzed, pathway of assembly intermediates in cells. Overall, we show how data obtained using a variety of techniques has led to our current understanding of HIV assembly.