Glycosylation patterns of HIV-1 gp120 depend on the type of expressing cells and affect antibody recognition.
Glycosylation patterns of HIV-1 gp120 depend on the type of expressing cells and affect antibody recognition.
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DOI：
10.1074/jbc.m109.085472
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发表时间：
2010-07-02
期刊：
影响因子：
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通讯作者：
Novak J
中科院分区：
文献类型：
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作者：
Raska M;Takahashi K;Czernekova L;Zachova K;Hall S;Moldoveanu Z;Elliott MC;Wilson L;Brown R;Jancova D;Barnes S;Vrbkova J;Tomana M;Smith PD;Mestecky J;Renfrow MB;Novak J
人类免疫缺陷病毒1型（HIV-1）的进入是由糖基化的包膜糖蛋白（gp 120）和宿主细胞受体之间的相互作用介导的。gp 120分子量的大约一半是由N-聚糖贡献的，N-聚糖作为潜在的表位，可以保护gp 120免受免疫识别。gp 120聚糖在宿主对HIV-1的免疫应答中的作用尚未在分子水平上进行全面研究。我们开发了一种新的方法来表征细胞特异性gp 120糖基化，糖基化的调节，以及可变糖基化对抗体反应性的影响。模型寡聚gp 120在不同的细胞类型中表达，包括代表宿主感染细胞或用于产生gp 120用于疫苗接种目的的细胞的细胞系。gp 120的N-糖基化变化，这取决于用于其表达的细胞类型和表达期间的代谢操作。所产生的糖基化包括高甘露糖与复合N-聚糖的比例、末端修饰和分支的变化。gp 120的差异糖基化影响了HIV-1感染者血清中多克隆抗体对包膜的识别。这些结果表明，gp 120聚糖有助于抗体反应性，并应在HIV-1疫苗设计中加以考虑。
Human immunodeficiency virus type 1 (HIV-1) entry is mediated by the interaction between a variably glycosylated envelope glycoprotein (gp120) and host-cell receptors. Approximately half of the molecular mass of gp120 is contributed by N-glycans, which serve as potential epitopes and may shield gp120 from immune recognition. The role of gp120 glycans in the host immune response to HIV-1 has not been comprehensively studied at the molecular level. We developed a new approach to characterize cell-specific gp120 glycosylation, the regulation of glycosylation, and the effect of variable glycosylation on antibody reactivity. A model oligomeric gp120 was expressed in different cell types, including cell lines that represent host-infected cells or cells used to produce gp120 for vaccination purposes. N-Glycosylation of gp120 varied, depending on the cell type used for its expression and the metabolic manipulation during expression. The resultant glycosylation included changes in the ratio of high-mannose to complex N-glycans, terminal decoration, and branching. Differential glycosylation of gp120 affected envelope recognition by polyclonal antibodies from the sera of HIV-1-infected subjects. These results indicate that gp120 glycans contribute to antibody reactivity and should be considered in HIV-1 vaccine design.