The mechanism of HIV-1 core assembly: Insights from three-dimensional reconstructions of authentic virions

The mechanism of HIV-1 core assembly: Insights from three-dimensional reconstructions of authentic virions
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DOI:
10.1016/j.str.2005.09.010
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发表时间:
2006-01-01
期刊:
影响因子:
5.7
通讯作者:
Fuller, SD
Fuller, SD
中科院分区:
生物学2区
文献类型:
--
作者:
Briggs, JAG;Gruenewald, K;Fuller, SD

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具有感染性的HIV颗粒含有一个特征的锥形核心,包裹着病毒RNA和复制蛋白。核心在大小和形状上表现出显著的异质性,但始终形成一个明确的结构。核心在成熟的病毒粒子中组装的机制仍然知之甚少。使用冷冻电子断层扫描,我们已经制作了真实的、未染色的HIV-1的三维重建。这些结果以前所未有的清晰度揭示了病毒的形态,并提出了细胞外病毒粒子内核心形成的以下机制:核心生长始于锥体的狭窄端,并向病毒粒子的远侧进行,直到被病毒膜限制。核心宽端的曲率和闭合则由病毒膜的内表面指示。这种机制在晶格生长方面提供了极大的灵活性,同时确保了不同大小和形状的核心的闭合。
Infectious HIV particles contain a characteristic cone-shaped core encasing the viral RNA and replication proteins. The core exhibits significant heterogeneity in size and shape, yet consistently forms a well-defined structure. The mechanism by which the core is assembled in the maturing virion remains poorly understood. Using cryo-electron tomography, we have produced three-dimensional reconstructions of authentic, unstained HIV-1. These reveal the viral morphology with unprecedented clarity and suggest the following mechanism for core formation inside the extracellular virion: core growth initiates at the narrow end of the cone and proceeds toward the distal side of the virion until limited by the viral membrane. Curvature and closure of the broad end of the core are then directed by the inner surface of the viral membrane. This mechanism accommodates significant flexibility in lattice growth while ensuring the closure of cores of variable size and shape.