HIV-2 Immature Particle Morphology Provides Insights into Gag Lattice Stability and Virus Maturation.
HIV-2 Immature Particle Morphology Provides Insights into Gag Lattice Stability and Virus Maturation.
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HIV-2 未成熟颗粒形态学提供了对 Gag 晶格稳定性和病毒成熟的见解。
DOI：
10.1016/j.jmb.2023.168143
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发表时间：
2023
影响因子：
5.6
通讯作者：
Zhang,Wei
中科院分区：
文献类型：
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作者：
Talledge,Nathaniel;Yang,Huixin;Shi,Ke;Coray,Raffaele;Yu,Guichuan;Arndt,WilliamG;Meng,Shuyu;Baxter,GloriaC;Mendonça,LuizaM;Castaño-Díez,Daniel;Aihara,Hideki;Mansky,LouisM;Zhang,Wei
逆转录病毒未成熟颗粒形态由膜封闭的、多形性的、球形的和不完整的Gag六聚体晶格组成。以前，我们证明了人类免疫缺陷病毒2型（HIV-2）的未成熟颗粒具有独特的和广泛的Gag晶格形态。为了更好地理解连续弯曲的六边形Gag晶格的性质，我们使用单粒子冷冻电子显微镜方法来确定未成熟病毒体的HIV-2 Gag晶格结构。5.5 μ m分辨率的重建图显示了稳定的酒杯形Gag六聚体结构，其结构特征与其他慢病毒未成熟Gag晶格结构一致。冷冻电子断层扫描提供了证据，几乎完全有序的Gag晶格结构的HIV-2未成熟的颗粒。我们还解析了HIV-2衣壳（CA）蛋白的羧基末端结构域（CTD）的1.98 nm分辨率晶体结构，该结构确定了在Gag的SP1区域不存在的情况下通过螺旋10的相互作用支持的结构化螺旋12。螺旋10-12界面上的残基被证明对维持HIV-2颗粒释放和感染性至关重要。总之，我们的研究结果提供了HIV-2未成熟Gag晶格的第一个3D组织，并对HIV Gag晶格稳定和病毒成熟提供了重要见解。
Retrovirus immature particle morphology consists of a membrane enclosed, pleomorphic, spherical and incomplete lattice of Gag hexamers. Previously, we demonstrated that human immunodeficiency virus type 2 (HIV-2) immature particles possess a distinct and extensive Gag lattice morphology. To better understand the nature of the continuously curved hexagonal Gag lattice, we have used the single particle cryo-electron microscopy method to determine the HIV-2 Gag lattice structure for immature virions. The reconstruction map at 5.5 Å resolution revealed a stable, wineglass-shaped Gag hexamer structure with structural features consistent with other lentiviral immature Gag lattice structures. Cryo-electron tomography provided evidence for nearly complete ordered Gag lattice structures in HIV-2 immature particles. We also solved a 1.98 Å resolution crystal structure of the carboxyl-terminal domain (CTD) of the HIV-2 capsid (CA) protein that identified a structured helix 12 supported via an interaction of helix 10 in the absence of the SP1 region of Gag. Residues at the helix 10–12 interface proved critical in maintaining HIV-2 particle release and infectivity. Taken together, our findings provide the first 3D organization of HIV-2 immature Gag lattice and important insights into both HIV Gag lattice stabilization and virus maturation.