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首页> 外文期刊>Journal of Molecular Biology >Characterization of the in vitro HIV-1 capsid assembly pathway.
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Characterization of the in vitro HIV-1 capsid assembly pathway.

机译：体外HIV-1衣壳装配途径的表征。

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摘要

During the morphogenesis of mature human immunodeficiency virus-1 cores, viral capsid proteins assemble conical or tubular shells around viral ribonucleoprotein complexes. This assembly step is mimicked in vitro through reactions in which capsid proteins oligomerize to form long tubes, and this process can be modeled as consisting of a slow nucleation period, followed by a rapid phase of tube growth. We have developed a novel fluorescence microscopy approach to monitor in vitro assembly reactions and have employed it, along with electron microscopy analysis, to characterize the assembly process. Our results indicate that temperature, salt concentration, and pH changes have differential effects on tube nucleation and growth steps. We also demonstrate that assembly can be unidirectional or bidirectional, that growth can be capped, and that proteins can assemble onto the surfaces of tubes, yielding multiwalled or nested structures. Finally, experiments show that a peptide inhibitor of in vitro assembly also can dismantle preexisting tubes, suggesting that such reagents may possess antiviral effects against both viral assembly and uncoating. Our investigations help establish a basis for understanding the mechanism of mature human immunodeficiency virus-1 core assembly and avenues for antiviral inhibition.
机译：在成熟的人类免疫缺陷病毒1核心的形态发生过程中，病毒衣壳蛋白围绕病毒核糖核蛋白复合物组装圆锥形或管状外壳。该装配步骤是通过衣壳蛋白寡聚形成长管的反应在体外模拟的，该过程可建模为缓慢的成核期，然后是快速的管生长阶段。我们已经开发出一种新颖的荧光显微镜方法来监测体外组装反应，并将其与电子显微镜分析一起用于表征组装过程。我们的结果表明温度，盐浓度和pH值变化对管形核和生长步骤具有不同的影响。我们还证明了组装可以是单向或双向的，生长可以被封闭，蛋白质可以组装在试管的表面，产生多壁或嵌套结构。最后，实验表明，体外组装的肽抑制剂还可以拆除先前存在的试管，这表明此类试剂可能对病毒组装和脱壳均具有抗病毒作用。我们的研究有助于建立基础，以了解成熟的人类免疫缺陷病毒1核心组装的机制和抗病毒抑制的途径。

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