HIV-1 gp120上PGT135抗体识别位点的聚糖微异质性揭示了中和抗性的分子机制。
Glycan Microheterogeneity at the PGT135 Antibody Recognition Site on HIV-1 gp120 Reveals a Molecular Mechanism for Neutralization Resistance.
作者信息
Pritchard Laura K, Spencer Daniel I R, Royle Louise, Vasiljevic Snezana, Krumm Stefanie A, Doores Katie J, Crispin Max
机构信息
Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford, United Kingdom.
Ludger Ltd., Culham Science Centre, Abingdon, Oxfordshire, United Kingdom.
出版信息
J Virol. 2015 Jul;89(13):6952-9. doi: 10.1128/JVI.00230-15. Epub 2015 Apr 15.
Abstract
Broadly neutralizing antibodies have been isolated that bind the glycan shield of the HIV-1 envelope spike. One such antibody, PGT135, contacts the intrinsic mannose patch of gp120 at the Asn332, Asn392, and Asn386 glycosylation sites. Here, site-specific glycosylation analysis of recombinant gp120 revealed glycan microheterogeneity sufficient to explain the existence of a minor population of virions resistant to PGT135 neutralization. Target microheterogeneity and antibody glycan specificity are therefore important parameters in HIV-1 vaccine design.
摘要
已经分离出能结合HIV-1包膜刺突聚糖屏蔽层的广泛中和抗体。其中一种抗体PGT135，在Asn332、Asn392和Asn386糖基化位点与gp120的内在甘露糖补丁接触。在此，重组gp120的位点特异性糖基化分析揭示了糖基微异质性，足以解释存在一小部分对PGT135中和具有抗性的病毒粒子。因此，靶点微异质性和抗体聚糖特异性是HIV-1疫苗设计中的重要参数。
相似文献
1
Glycan Microheterogeneity at the PGT135 Antibody Recognition Site on HIV-1 gp120 Reveals a Molecular Mechanism for Neutralization Resistance.HIV-1 gp120上PGT135抗体识别位点的聚糖微异质性揭示了中和抗性的分子机制。
J Virol. 2015 Jul;89(13):6952-9. doi: 10.1128/JVI.00230-15. Epub 2015 Apr 15.
2
Conserved Role of an N-Linked Glycan on the Surface Antigen of Human Immunodeficiency Virus Type 1 Modulating Virus Sensitivity to Broadly Neutralizing Antibodies against the Receptor and Coreceptor Binding Sites.人免疫缺陷病毒1型表面抗原上的N-连接聚糖在调节病毒对针对受体和共受体结合位点的广泛中和抗体敏感性方面的保守作用。
J Virol. 2015 Oct 28;90(2):829-41. doi: 10.1128/JVI.02321-15. Print 2016 Jan 15.
3
Structure-based, targeted deglycosylation of HIV-1 gp120 and effects on neutralization sensitivity and antibody recognition.基于结构的HIV-1 gp120靶向去糖基化及其对中和敏感性和抗体识别的影响。
Virology. 2003 Sep 1;313(2):387-400. doi: 10.1016/s0042-6822(03)00294-0.
4
Chinks in the armor of the HIV-1 Envelope glycan shield: Implications for immune escape from anti-glycan broadly neutralizing antibodies.人类免疫缺陷病毒1型包膜聚糖屏蔽层的漏洞：对逃避抗聚糖广泛中和抗体免疫的影响
Virology. 2017 Jan 15;501:12-24. doi: 10.1016/j.virol.2016.10.026. Epub 2016 Nov 13.
5
HIV-1 Glycan Density Drives the Persistence of the Mannose Patch within an Infected Individual.HIV-1聚糖密度驱动感染个体体内甘露糖补丁的持久性。
J Virol. 2016 Nov 28;90(24):11132-11144. doi: 10.1128/JVI.01542-16. Print 2016 Dec 15.
6
Mapping the complete glycoproteome of virion-derived HIV-1 gp120 provides insights into broadly neutralizing antibody binding.绘制完整的病毒衍生的 HIV-1 gp120 糖蛋白组图谱有助于深入了解广泛中和抗体的结合。
Sci Rep. 2016 Sep 8;6:32956. doi: 10.1038/srep32956.
7
Probability of N332 glycan occupancy on HIV-1 gp120 modulates sensitivity to broadly neutralizing antibodies.HIV-1 gp120上N332聚糖占据的概率调节对广泛中和抗体的敏感性。
AIDS. 2016 Sep 10;30(14):2179-84. doi: 10.1097/QAD.0000000000001177.
8
Anti-V3/Glycan and Anti-MPER Neutralizing Antibodies, but Not Anti-V2/Glycan Site Antibodies, Are Strongly Associated with Greater Anti-HIV-1 Neutralization Breadth and Potency.抗V3/聚糖和抗膜近端外部区域（MPER）中和抗体，而非抗V2/聚糖位点抗体，与更强的抗HIV-1中和广度和效力密切相关。
J Virol. 2015 May;89(10):5264-75. doi: 10.1128/JVI.00129-15. Epub 2015 Feb 11.
9
Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity.相邻 gp120 可变区 1 (V1) N-糖基化与中和敏感性相关，对 HIV-1 gp120-gp41 结合部位的变构调节。
PLoS Pathog. 2013;9(4):e1003218. doi: 10.1371/journal.ppat.1003218. Epub 2013 Apr 4.
10
A potent and broad neutralizing antibody recognizes and penetrates the HIV glycan shield.一种强效且广谱的中和抗体可识别并穿透 HIV 聚糖盾牌。
Science. 2011 Nov 25;334(6059):1097-103. doi: 10.1126/science.1213256. Epub 2011 Oct 13.
引用本文的文献
1
The HIV-1 envelope glycoprotein: structure, function and interactions with neutralizing antibodies.人类免疫缺陷病毒1型包膜糖蛋白：结构、功能及与中和抗体的相互作用
Nat Rev Microbiol. 2025 Jul 23. doi: 10.1038/s41579-025-01206-6.
2
Influence of glycosylation on the immunogenicity and antigenicity of viral immunogens.糖基化对病毒免疫原的免疫原性和抗原性的影响。
Biotechnol Adv. 2024 Jan-Feb;70:108283. doi: 10.1016/j.biotechadv.2023.108283. Epub 2023 Nov 14.
3
Glycan heterogeneity as a cause of the persistent fraction in HIV-1 neutralization.糖基异质性是 HIV-1 中和作用中持久性部分的原因。
PLoS Pathog. 2023 Oct 30;19(10):e1011601. doi: 10.1371/journal.ppat.1011601. eCollection 2023 Oct.
4
Conformational antigenic heterogeneity as a cause of the persistent fraction in HIV-1 neutralization.构象表位抗原异质性是 HIV-1 中和持续存在的原因。
Retrovirology. 2023 May 27;20(1):9. doi: 10.1186/s12977-023-00624-9.
5
Glycosylation and Serological Reactivity of an Expression-enhanced SARS-CoV-2 Viral Spike Mimetic.表达增强型 SARS-CoV-2 病毒刺突模拟物的糖基化和血清学反应性。
J Mol Biol. 2022 Jan 30;434(2):167332. doi: 10.1016/j.jmb.2021.167332. Epub 2021 Oct 27.
6
Analysis of the avian coronavirus spike protein reveals heterogeneity in the glycans present.分析禽冠状病毒的刺突蛋白揭示了存在的聚糖异质性。
J Gen Virol. 2021 Aug;102(8). doi: 10.1099/jgv.0.001642.
7
Networks of HIV-1 Envelope Glycans Maintain Antibody Epitopes in the Face of Glycan Additions and Deletions.HIV-1包膜聚糖网络在聚糖添加和缺失情况下维持抗体表位
Structure. 2020 Aug 4;28(8):897-909.e6. doi: 10.1016/j.str.2020.04.022. Epub 2020 May 19.
8
Similarities and differences between native HIV-1 envelope glycoprotein trimers and stabilized soluble trimer mimetics.天然 HIV-1 包膜糖蛋白三聚体与稳定可溶性三聚体模拟物之间的相似性和差异。
PLoS Pathog. 2019 Jul 15;15(7):e1007920. doi: 10.1371/journal.ppat.1007920. eCollection 2019 Jul.
9
Protein and Glycan Mimicry in HIV Vaccine Design.蛋白质和糖基模拟在 HIV 疫苗设计中的应用。
J Mol Biol. 2019 May 31;431(12):2223-2247. doi: 10.1016/j.jmb.2019.04.016. Epub 2019 Apr 24.
10
HIV-1 envelope glycan modifications that permit neutralization by germline-reverted VRC01-class broadly neutralizing antibodies.HIV-1 包膜糖基化修饰可被 VRC01 类种系返回复性的广泛中和抗体中和。
PLoS Pathog. 2018 Nov 5;14(11):e1007431. doi: 10.1371/journal.ppat.1007431. eCollection 2018 Nov.
本文引用的文献
1
Two classes of broadly neutralizing antibodies within a single lineage directed to the high-mannose patch of HIV envelope.同一谱系内两类针对HIV包膜高甘露糖区域的广泛中和抗体。
J Virol. 2015 Jan 15;89(2):1105-18. doi: 10.1128/JVI.02905-14. Epub 2014 Nov 5.
2
Structural evolution of glycan recognition by a family of potent HIV antibodies.一类强效HIV抗体对聚糖识别的结构演变
Cell. 2014 Sep 25;159(1):69-79. doi: 10.1016/j.cell.2014.09.009.
3
Broad and potent HIV-1 neutralization by a human antibody that binds the gp41-gp120 interface.一种结合gp41-gp120界面的人源抗体对HIV-1具有广泛且强效的中和作用。
Nature. 2014 Nov 6;515(7525):138-42. doi: 10.1038/nature13601. Epub 2014 Sep 3.
4
Structure of 2G12 Fab2 in complex with soluble and fully glycosylated HIV-1 Env by negative-stain single-particle electron microscopy.通过负染单颗粒电子显微镜观察2G12 Fab2与可溶性全糖基化HIV-1包膜蛋白复合物的结构。
J Virol. 2014 Sep 1;88(17):10177-88. doi: 10.1128/JVI.01229-14. Epub 2014 Jun 25.
5
Promiscuous glycan site recognition by antibodies to the high-mannose patch of gp120 broadens neutralization of HIV.抗体对 gp120 高甘露糖补丁的混杂糖基位点识别可扩大对 HIV 的中和作用。
Sci Transl Med. 2014 May 14;6(236):236ra63. doi: 10.1126/scitranslmed.3008104.
6
Structural delineation of a quaternary, cleavage-dependent epitope at the gp41-gp120 interface on intact HIV-1 Env trimers.在完整的 HIV-1 Env 三聚体上，gp41-gp120 界面处的一个四分体、依赖裂解的表位的结构描绘。
Immunity. 2014 May 15;40(5):669-80. doi: 10.1016/j.immuni.2014.04.008. Epub 2014 Apr 24.
7
Broadly neutralizing HIV antibodies define a glycan-dependent epitope on the prefusion conformation of gp41 on cleaved envelope trimers.广谱中和 HIV 抗体定义了 gp41 融合前构象上糖依赖性表位在裂解包膜三聚体上。
Immunity. 2014 May 15;40(5):657-68. doi: 10.1016/j.immuni.2014.04.009. Epub 2014 Apr 24.
8
Antibody 8ANC195 reveals a site of broad vulnerability on the HIV-1 envelope spike.抗体8ANC195揭示了HIV-1包膜刺突上一个广泛易损位点。
Cell Rep. 2014 May 8;7(3):785-95. doi: 10.1016/j.celrep.2014.04.001. Epub 2014 Apr 24.
9
Crystal structure of a soluble cleaved HIV-1 envelope trimer.可溶性 HIV-1 包膜三聚体的晶体结构
Science. 2013 Dec 20;342(6165):1477-83. doi: 10.1126/science.1245625. Epub 2013 Oct 31.
10
Therapeutic efficacy of potent neutralizing HIV-1-specific monoclonal antibodies in SHIV-infected rhesus monkeys.高效中和 HIV-1 特异性单克隆抗体在感染猴免疫缺陷病毒的恒河猴中的治疗效果。
Nature. 2013 Nov 14;503(7475):224-8. doi: 10.1038/nature12744. Epub 2013 Oct 30.
Zotero 插件