Human milk oligosaccharides reduce HIV-1-gp120 binding to dendritic cell-specific ICAM3-grabbing non-integrin (DC-SIGN)
Human milk oligosaccharides reduce HIV-1-gp120 binding to dendritic cell-specific ICAM3-grabbing non-integrin (DC-SIGN)
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DOI：
10.1017/s0007114508025804
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发表时间：
2009-02-28
影响因子：
3.6
通讯作者：
Bode, Lars
中科院分区：
文献类型：
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作者：
Hong, Patrick;Ninonuevo, Milady R.;Bode, Lars
母乳喂养是儿童感染HIV-1的主要产后传播途径。然而，大多数母乳喂养的婴儿尽管在数月内通过母乳持续接触艾滋病毒，但并没有感染艾滋病毒。什么可以保护母乳喂养的婴儿免受HIV-1感染？HIV-1穿过婴儿粘膜屏障的部分介导是通过HIV-1表面糖蛋白gp 120与人树突状细胞上的树突状细胞特异性ICAM 3抓取非整合素（DC-SIGN）的结合。存在于人乳中的刘易斯抗原聚糖与DC-SIGN结合并抑制HIV-1转移至CD 4 + T淋巴细胞。人乳中含有大量未结合的复合寡糖（5- 10 g/l），这些寡糖携带一个或多个刘易斯抗原聚糖，我们假设它们与gp 120竞争DC-SIGN结合。在这里，我们在两个独立的试验中表明，人乳低聚糖的生理浓度显着降低gp 120结合DC-SIGN超过80%。这些结果可能为母乳对HIV-1母婴传播的抑制作用提供了额外的解释。确定与DC-SIGN相互作用的特定牛奶低聚糖可以指导基于聚糖的药物的开发，这些药物可以防止HIV-1和其他使用DC-SIGN作为切入点的病原体的传播。然而，阻止DC-SIGN可能是一把双刃剑。
Breast-feeding is the predominant postnatal transmission route for HIV-1 infection in children. However, a majority of breast-fed infants do not become HlV-infected despite continuous exposure to the virus through their mothers' milk over many months. What protects some breast-fed infants from HIV-1 infection? HIV-1 entry across the infant's mucosal barrier is partially mediated through binding of the HIV-1 surface glycoprotein gp120 to dendritic cell-specific ICAM3-grabbing non-integrin (DC-SIGN) on human dendritic cells. Lewis antigen glycans, present in human milk, bind to DC-SIGN and inhibit HIV-1 transfer to CD4 + T lymphocytes. Human milk contains a high amount of unbound, complex oligosaccharides (5-10g/l) that carry one or more Lewis antigen glycans, and we hypothesized that they compete with gp120 for DC-SIGN binding. Here, we show in two independent assays that physiological concentrations of human milk oligosaccharides significantly reduce gp120 binding to DC-SIGN by more than 80%. These results may provide an additional explanation for the inhibitory effects of human milk on HIV-1 mother-to-child-transmission. Identifying the specific milk oligosaccharides that interact with DC-SIGN may guide the development of glycan-based drugs that prevent transmission of HIV-1 and other pathogens that use DC-SIGN as an entry point. However, blocking DC-SIGN may be a two-edged sword.