Composition and Antigenic Effects of Individual Glycan Sites of a Trimeric HIV-1 Envelope Glycoprotein.
Composition and Antigenic Effects of Individual Glycan Sites of a Trimeric HIV-1 Envelope Glycoprotein.
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DOI：
10.1016/j.celrep.2016.02.058
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发表时间：
2016-03-22
期刊：
影响因子：
8.8
通讯作者：
Crispin M
中科院分区：
文献类型：
--
作者：
Behrens AJ;Vasiljevic S;Pritchard LK;Harvey DJ;Andev RS;Krumm SA;Struwe WB;Cupo A;Kumar A;Zitzmann N;Seabright GE;Kramer HB;Spencer DI;Royle L;Lee JH;Klasse PJ;Burton DR;Wilson IA;Ward AB;Sanders RW;Moore JP;Doores KJ;Crispin M
HIV-1包膜糖蛋白三聚体被一系列N-连接的聚糖覆盖，这些聚糖使其免受免疫监视。三聚体表面上的高密度聚糖施加了限制聚糖加工酶的作用的空间约束，使得多个加工不足的结构保留在特定区域上。这些寡聚甘露糖聚糖被广泛中和抗体（bNAb）识别，这些抗体不会被聚糖屏蔽所阻碍，但矛盾的是，靶向它。我们对可溶性重组三聚体（BG 505 SOSIP.664）的位点特异性糖基化分析绘制了单个位点聚糖加工的简单性和多样性的极端，并揭示了外部结构域上密集的寡聚甘露糖聚糖簇的马赛克。虽然个别网站通常最低限度地影响全球完整性的聚糖盾，我们确定的例子，删除一些聚糖可以微妙地影响中和bNAb结合在遥远的网站。bNAb靶向聚糖的网络应保留在疫苗抗原上。可溶性HIV-1 Env三聚体的位点特异性N-聚糖定量分析单个聚糖位点简单性和多样性的极端图谱Env三聚体甘露糖斑块区域的精细结构单个聚糖位点如何影响HIV-1 Env-假病毒中和Behrens et al.目前详细的，定量的，位点特异性分析的N-糖基化位点的可溶性重组HIV-1包膜糖蛋白三聚体。这些结果突出了聚糖盾的结构和抗原细节，这对于设计下一代HIV-1 Env疫苗和了解广泛活性抗体的病毒中和作用是有价值的。
The HIV-1 envelope glycoprotein trimer is covered by an array of N-linked glycans that shield it from immune surveillance. The high density of glycans on the trimer surface imposes steric constraints limiting the actions of glycan-processing enzymes, so that multiple under-processed structures remain on specific areas. These oligomannose glycans are recognized by broadly neutralizing antibodies (bNAbs) that are not thwarted by the glycan shield but, paradoxically, target it. Our site-specific glycosylation analysis of a soluble, recombinant trimer (BG505 SOSIP.664) maps the extremes of simplicity and diversity of glycan processing at individual sites and reveals a mosaic of dense clusters of oligomannose glycans on the outer domain. Although individual sites usually minimally affect the global integrity of the glycan shield, we identify examples of how deleting some glycans can subtly influence neutralization by bNAbs that bind at distant sites. The network of bNAb-targeted glycans should be preserved on vaccine antigens. Quantitative, site-specific N-glycan analysis of a soluble HIV-1 Env trimer A map of the extremes of simplicity and diversity at individual glycan sites The fine structure of the mannose patch area of the Env trimer How individual glycan sites influence HIV-1 Env-pseudovirus neutralization Behrens et al. present detailed, quantitative, site-specific analyses of N-glycosylation sites of a soluble recombinant HIV-1 envelope glycoprotein trimer. The results highlight structural and antigenic details of the glycan shield that will be valuable for designing next-generation HIV-1 Env vaccines and understanding virus neutralization by broadly active antibodies.