Glycomic characterization of respiratory tract tissues of ferrets: implications for its use in influenza virus infection studies.
Glycomic characterization of respiratory tract tissues of ferrets: implications for its use in influenza virus infection studies.
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DOI：
10.1074/jbc.m114.588541
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发表时间：
2014-10-10
期刊：
影响因子：
--
通讯作者：
Haslam SM
中科院分区：
文献类型：
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作者：
Jia N;Barclay WS;Roberts K;Yen HL;Chan RW;Lam AK;Air G;Peiris JS;Dell A;Nicholls JM;Haslam SM
背景：雪貂是研究流感病毒传播特性的重要动物模型。结果：雪貂呼吸道组织鉴定鉴定出流感病毒多糖受体。结论：获得了具有种属特异性的流感病毒糖链受体。意义：我们的发现为雪貂在流感病毒感染研究中的有用性提供了新的见解。流感病毒和宿主细胞之间的初始识别是通过病毒表面蛋白血凝素和宿主细胞表面唾液酸终止的糖偶联物之间的相互作用来实现的。唾液酸残基可以通过α2-3-或α2-6型糖苷键与相邻的单糖相连。正是这种连锁差异主要定义了流感病毒感染的物种屏障，α2-3结合与禽流感病毒有关，α2-6结合与人类毒株有关。雪貂已被广泛用作研究流感传播的动物模型。为了更好地理解这个模型系统的有效性，我们对雪貂的呼吸组织进行了血糖表征，这使得可以在人类和雪貂之间进行潜在的病毒受体的比较。为了补充结构分析，进行了凝集素染色实验，以表征多糖在雪貂呼吸道中的区域分布。最后，通过多聚糖阵列实验评估了所鉴定的多聚糖与不同流感病毒株的血凝素的结合情况。我们的结果表明，雪貂的呼吸组织异质性地表达α2-3-和α2-6连接的唾液酸。然而，雪貂的呼吸道组织也表达SDA表位(NeuAcα2-3(GalNAcβ1-4)GalGalβ1-4GlcNAc)和唾液酸化N，N‘-二乙酰乳糖胺(NeuAcα2-6GalNAcβ1-4GlcNAc)，这在人呼吸道表面上皮细胞中没有观察到。SDA表位的存在减少了禽类病毒的潜在结合部位，因此可能对雪貂在流感病毒感染研究中的应用具有一定的意义。
Background: The ferret is a key animal model to study the transmission characteristics of influenza viruses. Results: Characterization of ferret respiratory tract tissues identified influenza virus glycan receptors. Conclusion: Species-specific influenza virus glycan receptors were identified. Significance: Our findings provide new insights into the usefulness of ferrets in the study of influenza virus infection. The initial recognition between influenza virus and the host cell is mediated by interactions between the viral surface protein hemagglutinin and sialic acid-terminated glycoconjugates on the host cell surface. The sialic acid residues can be linked to the adjacent monosaccharide by α2–3- or α2–6-type glycosidic bonds. It is this linkage difference that primarily defines the species barrier of the influenza virus infection with α2–3 binding being associated with avian influenza viruses and α2–6 binding being associated with human strains. The ferret has been extensively used as an animal model to study the transmission of influenza. To better understand the validity of this model system, we undertook glycomic characterization of respiratory tissues of ferret, which allows a comparison of potential viral receptors to be made between humans and ferrets. To complement the structural analysis, lectin staining experiments were performed to characterize the regional distributions of glycans along the respiratory tract of ferrets. Finally, the binding between the glycans identified and the hemagglutinins of different strains of influenza viruses was assessed by glycan array experiments. Our data indicated that the respiratory tissues of ferret heterogeneously express both α2–3- and α2–6-linked sialic acids. However, the respiratory tissues of ferret also expressed the Sda epitope (NeuAcα2-3(GalNAcβ1–4)Galβ1–4GlcNAc) and sialylated N,N′-diacetyllactosamine (NeuAcα2–6GalNAcβ1–4GlcNAc), which have not been observed in the human respiratory tract surface epithelium. The presence of the Sda epitope reduces potential binding sites for avian viruses and thus may have implications for the usefulness of the ferret in the study of influenza virus infection.