Assembly and architecture of HIV.

Assembly and architecture of HIV.
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DOI:
10.1007/978-1-4614-0980-9_20
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发表时间:
2012
影响因子:
--
通讯作者:
Pornillos O
Pornillos O
中科院分区:
医学4区
文献类型:
--
作者:
Ganser-Pornillos BK;Yeager M;Pornillos O

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HIV形成球形、有膜包膜、多形性病毒粒子,直径1,000 - 1,500 μ m,其中含有两个拷贝的单链、正义RNA基因组。病毒颗粒最初以非感染性或不成熟的形式从宿主细胞中出芽,其中基因组进一步封装在由约2,500个病毒编码的Gag多聚蛋白拷贝组成的球形蛋白质壳内。Gag分子呈放射状排列,粘附在病毒膜的内叶上,并紧密结合为六边形的准晶体晶格。Gag包含三个主要结构域,称为MA、CA和NC。对于未成熟的病毒体变得具有感染性,它们必须经历成熟过程,该成熟过程由病毒蛋白酶对Gag的蛋白水解加工引发。新的GAG衍生的蛋白质经历戏剧性的重排,形成成熟的病毒。成熟的MA蛋白形成一个“基质”层,并保持附着在病毒包膜上,NC与基因组缩合,大约1,500个CA拷贝组装成一个新的锥形蛋白壳,称为成熟衣壳,它包围着基因组核糖核蛋白复合物。HIV衣壳符合富勒烯壳的数学原理,其中CA亚单位形成约250个CA六聚体,排列在弯曲的六边形晶格上,该晶格通过恰好12个五聚体的掺入而闭合,其中7个五聚体在圆锥体的宽端,5个在圆锥体的窄端。本章描述了我们目前对HIV病毒体结构及其动态转变的理解:由Gag编排的病毒体组装过程,未成熟病毒体的结构,病毒成熟过程和成熟衣壳的结构。
HIV forms spherical, membrane-enveloped, pleomorphic virions, 1,000–1,500 Å in diameter, which contain two copies of its single-stranded, positive-sense RNA genome. Virus particles initially bud from host cells in a noninfectious or immature form, in which the genome is further encapsulated inside a spherical protein shell composed of around 2,500 copies of the virally encoded Gag polyprotein. The Gag molecules are radially arranged, adherent to the inner leaflet of the viral membrane, and closely associated as a hexagonal, paracrystalline lattice. Gag comprises three major structural domains called MA, CA, and NC. For immature virions to become infectious, they must undergo a maturation process that is initiated by proteolytic processing of Gag by the viral protease. The new Gag-derived proteins undergo dramatic rearrangements to form the mature virus. The mature MA protein forms a “matrix” layer and remains attached to the viral envelope, NC condenses with the genome, and approximately 1,500 copies of CA assemble into a new cone-shaped protein shell, called the mature capsid, which surrounds the genomic ribonucleoprotein complex. The HIV capsid conforms to the mathematical principles of a fullerene shell, in which the CA sub-units form about 250 CA hexamers arrayed on a variably curved hexagonal lattice, which is closed by incorporation of exactly 12 pentamers, seven pentamers at the wide end and five at the narrow end of the cone. This chapter describes our current understanding of HIV’s virion architecture and its dynamic transformations: the process of virion assembly as orchestrated by Gag, the architecture of the immature virion, the virus maturation process, and the structure of the mature capsid.
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