Glycan microarray analysis of the hemagglutinins from modern and pandemic influenza viruses reveals different receptor specificities
Glycan microarray analysis of the hemagglutinins from modern and pandemic influenza viruses reveals different receptor specificities
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DOI：
10.1016/j.jmb.2005.11.002
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发表时间：
2006-02-03
影响因子：
5.6
通讯作者：
Wilson, IA
中科院分区：
文献类型：
--
作者：
Stevens, J;Blixt, O;Wilson, IA
甲型流感病毒对宿主的特异性是由病毒表面糖蛋白血凝素（HA）介导的，HA与含有末端唾液酸聚糖的受体结合。禽病毒优先结合肠上皮细胞受体上的α 2-3链唾液酸，而人病毒特异性结合肺和上呼吸道上皮细胞上的α 2-6链。为了确定许多人类和禽类H1和H3病毒（包括1918年H1N1大流行毒株）的受体偏好，使用最近描述的聚糖阵列分析了它们的血凝素。该阵列包含200种碳水化合物和糖蛋白，不仅揭示了受体对α - 2-3和/或α - 2-6唾液酸连锁的明显差异，而且还可以检测到HA特异性的细微差异，例如对末端三糖2 （Gal）和3 （GlcNAc, GalNAc）位置的聚焦化、硫酸化和唾液化的偏好。对于1918年的两种HA变体，南卡罗莱纳HA (SC)（含Asp190和Asp225）只结合α 2-6受体，而纽约HA （NY）变体只有一个残基（Gly225）不同，具有混合α 2-6/ α 2-3特异性，特别是对硫酸低聚糖。仅一个NY变异（Asp190Glu）突变就足以使HA受体偏好恢复到经典禽毒株的偏好。因此，物种屏障（由1918年人类病毒与可能的禽病毒祖病毒相比的受体特异性偏好所定义）只能通过HA受体结合位点的两个位置的改变来绕过。因此，聚糖阵列提供了流感受体特异性的非常详细的概况，可用于绘制新的人类致病毒株（如H5N1禽流感）的进化图谱。(c) Elsevier Ltd.版权所有。
Influenza A virus specificity for the host is mediated by the viral surface glycoprotein hemagglutinin (HA), which binds to receptors containing glycans with terminal sialic acids. Avian viruses preferentially bind to alpha 2-3-linked sialic acids on receptors of intestinal epithelial cells, whereas human viruses are specific for the alpha 2-6 linkage on epithelial cells of the lungs and upper respiratory tract. To define the receptor preferences of a number of human and avian H1 and H3 viruses, including the 1918 H1N1 pandemic strains, their hemagglutinins were analyzed using a recently described glycan array. The array, which contains 200 carbohydrates and glycoproteins, not only revealed clear differentiation of receptor preferences for alpha 2-3 and/or alpha 2-6 sialic acid linkage, but could also detect fine differences in HA specificity, such as preferences for fucosylation, sulfation and sialylation at positions 2 (Gal) and 3 (GlcNAc, GalNAc) of the terminal trisaccharide. For the two 1918 HA variants, the South Carolina (SC) HA (with Asp190, Asp225) bound exclusively alpha 2-6 receptors, while the New York (NY) variant, which differed only by one residue (Gly225), had mixed alpha 2-6/alpha 2-3 specificity, especially for sulfated oligosaccharides. Only one mutation of the NY variant (Asp190Glu) was sufficient to revert the HA receptor preference to that of classical avian strains. Thus, the species barrier, as defined by the receptor specificity preferences of 1918 human viruses compared to likely avian virus progenitors, can be circumvented by changes at only two positions in the HA receptor binding site. The glycan array thus provides highly detailed profiles of influenza receptor specificity that can be used to map the evolution of new human pathogenic strains, such as the H5N1 avian influenza. (c) Elsevier Ltd. All rights reserved.