Division of Virology, Department of Clinical Microbiology, Umeå University, SE-90185 Umeå, Sweden.
J Virol. 2011 Nov;85(21):11283-90. doi: 10.1128/JVI.05597-11. Epub 2011 Aug 31.
Coxsackievirus A24 variant (CVA24v) is a main causative agent of acute hemorrhagic conjunctivitis (AHC), which is a highly contagious eye infection. Previously it has been suggested that CVA24v uses sialic acid-containing glycoconjugates as attachment receptors on corneal cells, but the nature of these receptors is poorly described. Here, we set out to characterize and identify the cellular components serving as receptors for CVA24v. Binding and infection experiments using corneal cells treated with deglycosylating enzymes or metabolic inhibitors of de novo glycosylation suggested that the receptor(s) used by CVA24v are constituted by sialylated O-linked glycans that are linked to one or more cell surface proteins but not to lipids. CVA24v bound better to mouse L929 cells overexpressing human P-selectin glycoprotein ligand-1 (PSGL-1) than to mock-transfected cells, suggesting that PSGL-1 is a candidate receptor for CVA24v. Finally, binding competition experiments using a library of mono- and oligosaccharides mimicking known PSGL-1 glycans suggested that CVA24v binds to Neu5Acα2,3Gal disaccharides (Neu5Ac is N-acetylneuraminic acid). These results provide further insights into the early steps of the CVA24v life cycle.
柯萨奇病毒 A24 变体（CVA24v）是急性出血性结膜炎（AHC）的主要病原体，AHC 是一种高度传染性的眼部感染。此前有研究表明，CVA24v 利用含有唾液酸的糖缀合物作为角膜细胞上的附着受体，但这些受体的性质描述得很差。在这里，我们着手表征和鉴定作为 CVA24v 受体的细胞成分。使用经糖基化酶处理或从头糖基化代谢抑制剂处理的角膜细胞进行的结合和感染实验表明，CVA24v 使用的受体由唾液酸化的 O-连接糖组成，这些糖与一个或多个细胞表面蛋白而非脂质相连。CVA24v 与过表达人 P 选择素糖蛋白配体 1（PSGL-1）的小鼠 L929 细胞的结合比 mock 转染细胞更好，这表明 PSGL-1 是 CVA24v 的候选受体。最后，使用模拟已知 PSGL-1 聚糖的单糖和寡糖文库进行的结合竞争实验表明，CVA24v 结合 Neu5Acα2,3Gal 二糖（Neu5Ac 是 N-乙酰神经氨酸）。这些结果进一步深入了解了 CVA24v 生命周期的早期步骤。
