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Isolation and characterisation of potential respiratory syncytial virus receptor(s) on epithelial cells

机译:上皮细胞上潜在的呼吸道合胞病毒受体的分离和鉴定

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Respiratory syncytial virus (RSV) infection causes severe lower respiratory diseases in infancy, early childhood and the elderly. RSV infections respond poorly to current therapies. Therefore, we initiated a search for novel drug targets by investigating the characteristics and identify of RSV adhesion receptors on mammalian cells. Soluble human lectins, complex polysaccharides and a low molecular selectin antagonist, TBC1269, were used to characterise and isolate the RSV receptor on a human epithelial cell line (Hep2 cells). The binding characteristics of the RSV receptor of Hep2 cells were similar to those reported for L-selectin. The carbohydrate-based selectin antagonists, fucoidan and TBC 1269, inhibit RSV infection both in vitro and in a mouse model of infection. Furthermore, we have isolated anmexin II as a potential RSV receptor on Hep2 cells. The expression of annexin II was increased after RSV infection. Recombinant annexin II binds to RSV G-protein, heparin and plasminogen and the binding is inhibited by a selectin antagonist, TBC1269, These findings in dicate that inhibitors of annexin II could have potential in treating RSV infection.
机译:呼吸道合胞病毒(RSV)感染在婴儿,幼儿和老年人中引起严重的下呼吸道疾病。 RSV感染对当前疗法的反应较差。因此,我们通过研究哺乳动物细胞中RSV粘附受体的特征和鉴定,开始寻找新的药物靶标。可溶性人类凝集素,复合多糖和低分子选择素拮抗剂TBC1269用于表征和分离人类上皮细胞系(Hep2细胞)上的RSV受体。 Hep2细胞的RSV受体的结合特性与L-选择蛋白的结合特性相似。基于碳水化合物的选择素拮抗剂岩藻依聚糖和TBC 1269在体外和小鼠感染模型中均抑制RSV感染。此外,我们已经分离出Anmexin II作为Hep2细胞上的潜在RSV受体。 RSV感染后膜联蛋白II的表达增加。重组膜联蛋白II与RSV G蛋白,肝素和纤溶酶原结合,并且该结合受到选择蛋白拮抗剂TBC1269的抑制。这些发现表明,膜联蛋白II抑制剂可能具有治疗RSV感染的潜力。

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