Behrens Anna-Janina, Vasiljevic Snezana, Pritchard Laura K, Harvey David J, Andev Rajinder S, Krumm Stefanie A, Struwe Weston B, Cupo Albert, Kumar Abhinav, Zitzmann Nicole, Seabright Gemma E, Kramer Holger B, Spencer Daniel I R, Royle Louise, Lee Jeong Hyun, Klasse Per J, Burton Dennis R, Wilson Ian A, Ward Andrew B, Sanders Rogier W, Moore John P, Doores Katie J, Crispin Max
Oxford Glycobiology Institute and Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
Department of Infectious Diseases, Faculty of Life Sciences and Medicine, King's College London, Guy's Hospital, London SE1 9RT, UK.
Cell Rep. 2016 Mar 22;14(11):2695-706. doi: 10.1016/j.celrep.2016.02.058. Epub 2016 Mar 10.
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.
HIV-1包膜糖蛋白三聚体被一系列N-连接聚糖所覆盖，这些聚糖使其免受免疫监视。三聚体表面聚糖的高密度造成空间位阻，限制了聚糖加工酶的作用，因此多个加工不完全的结构保留在特定区域。这些寡甘露糖聚糖可被广泛中和抗体（bNAbs）识别，这些抗体不会被聚糖屏蔽所阻碍，反而以其为靶点。我们对可溶性重组三聚体（BG505 SOSIP.664）进行的位点特异性糖基化分析，绘制了各个位点聚糖加工的简单性和多样性的极端情况，并揭示了在外结构域上寡甘露糖聚糖密集簇的镶嵌图。尽管单个位点通常对聚糖屏蔽的整体完整性影响最小，但我们发现了一些例子，说明删除某些聚糖会如何微妙地影响在远处位点结合的bNAbs的中和作用。疫苗抗原上应保留bNAb靶向聚糖的网络。
