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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Envelope glycans of immunodeficiency virions are almost entirely oligomannose antigens
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Envelope glycans of immunodeficiency virions are almost entirely oligomannose antigens

机译：免疫缺陷病毒粒子的包膜聚糖几乎完全是寡甘露糖抗原

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摘要

The envelope spike of HIV is one of the most highly N-glycosylated structures found in nature. However, despite extensive research revealing essential functional roles in infection and immune evasion, the chemical structures of the glycans on the native viral envelope glycoprotein gp120-as opposed to recombinantly generated gp120 -have not been described. Here, we report on the identity of the N-linked glycans from primary isolates of HIV-1 (clades A, B, and C) and from the simian immunodeficiency virus. MS analysis reveals a remarkably simple and highly conserved virus-specific glycan profile almost entirely devoid of medial Golgi-mediated processing. In stark contrast to recombinant gp120, which shows extensive exposure to cellular glycosylation enzymes (>70% complex type glycans), the native envelope shows barely detectable processing beyond the bio-synthetic intermediate Man_5GIcNAc_2 (<2% complex type glycans). This oligomannose (Man_(5-9)GIcNAc_2) profile is conserved across primary isolates and geographically divergent clades but is not reflected in the current generation of gp120 antigens used for vaccine trials. In the context of vaccine design, we also note that Manα1→2Man-terminating glycans (Man_(6-9)GIcNAc_2) of the type recognized by the broadly neutralizing anti-HIV antibody 2G12 are 3-fold more abundant on the native envelope than on the recombinant monomer and are also found on isolates not neutralized by 2G12. The Manα1→2-Man residues of gp120 therefore provide a vaccine target that is physically larger and antigenically more conserved than the 2G12 epitope itself. This study revises and extends our understanding of the glycan shield of HIV with implications for AIDS vaccine design.
机译：HIV的包膜尖峰是自然界中最高度N-糖基化的结构之一。然而，尽管广泛的研究揭示了在感染和免疫逃避中的基本功能作用，但是与重组产生的gp120相反，天然病毒包膜糖蛋白gp120上的聚糖的化学结构尚未被描述。在这里，我们从HIV-1的主要分离株（A，B和C株）和猿猴免疫缺陷病毒报告了N-连接聚糖的身份。 MS分析显示了一个非常简单且高度保守的病毒特异性聚糖谱，几乎完全没有中间的高尔基体介导的加工。与重组gp120形成鲜明对比，重组gp120显示广泛暴露于细胞糖基化酶（> 70％复杂类型的聚糖），其天然包膜显示出几乎无法检测到超过生物合成中间体Man_5GIcNAc_2（<2％复杂类型的聚糖）的过程。该低聚甘露糖（Man_（5-9）GIcNAc_2）图谱在主要分离株和地理上不同的进化枝中均保守，但未反映在当前用于疫苗试验的gp120抗原中。在疫苗设计的背景下，我们还注意到，被广泛中和的抗HIV抗体2G12识别的Manα1→2Man端聚糖（Man_（6-9）GIcNAc_2）比天然包膜多3倍的丰富度可以在重组单体上使用，也可以在未被2G12中和的分离物中找到。因此，gp120的Manα1→2-Man残基提供的疫苗靶标比2G12表位本身在物理上更大，在抗原上更保守。这项研究修订并扩展了我们对HIV的聚糖屏蔽的理解，并对AIDS疫苗设计产生了影响。

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    Katie J. Doores; rnCamille Bonomelli; rnDavid J. Harvey; rnSnezana Vasiljevic; rnRaymond A. Dwek; rnDennis R. Burton; Max Crispin; rnChristopher N. Scanlan;

  • 作者单位

    Department of Immunology and Microbial Science and International AIDS Vaccine Initiative Neutralizing Antibody Center, The cripps Research Institute, La Jolla, CA 92037 The Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Boston, MA 02114;

    rnOxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, United Kingdom;

    rnOxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, United Kingdom;

    rnOxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, United Kingdom;

    rnOxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, United Kingdom;

    rnDepartment of Immunology and Microbial Science and International AIDS Vaccine Initiative Neutralizing Antibody Center, The cripps Research Institute, La Jolla, CA 92037 The Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Boston, MA 02114;

    rnOxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, United Kingdom;

    rnOxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, United Kingdom;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
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  • 关键词

    HIV; 2G12; gp120; glycosylation; vaccine;

    机译：艾滋病病毒;2G12;gp120;糖基化疫苗;

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