Human P-selectin glycoprotein ligand-1 is a functional receptor for enterovirus 71
Human P-selectin glycoprotein ligand-1 is a functional receptor for enterovirus 71
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DOI：
10.1038/nm.1961
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发表时间：
2009-07-01
期刊：
影响因子：
82.9
通讯作者：
Shimizu, Hiroyuki
中科院分区：
文献类型：
--
作者：
Nishimura, Yorihiro;Shimojima, Masayuki;Shimizu, Hiroyuki
肠病毒71型（EV71）是手足口病的主要病原体，手足口病是一种常见于幼儿的发热性疾病。虽然手足口病的临床表现通常是轻微和自限性的，但严重的肠病毒71型暴发可导致多种神经系统疾病。鉴定特异性细胞受体对于阐明早期病毒-宿主相互作用机制和肠病毒发病机制至关重要(1)。在这里，我们通过筛选的表达克隆方法鉴定了人p -选择素糖蛋白配体-1 (PSGL-1; CD162)，一种在白细胞上表达的唾液黏液蛋白膜蛋白，在炎症的早期阶段发挥重要作用（2-4），作为EV71的功能性受体(5)。PSGL-1的n端特异结合EV71。稳定的PSGL-1表达允许EV71进入和复制，并在非易感小鼠L929细胞中产生细胞病变效应。8个EV71菌株中有5个结合可溶性PSGL-1，并使用完整的PSGL-1作为Jurkat T细胞感染的主要受体。另外三株EV71病毒株没有使用PSGL-1，这表明EV71病毒在白细胞中存在菌株特异性复制。EV71在非白细胞细胞系中以不依赖于psgl -1的方式复制，表明存在EV71的替代受体。PSGL-1作为EV71受体的鉴定为PSGL-1阳性白细胞在手足口病和其他EV71介导的疾病过程中的细胞向性和发病机制中的作用提供了新的线索。
Enterovirus 71 (EV71) is a major causative agent of hand, foot and mouth disease (HFMD), a common febrile disease occurring mainly in young children. Although clinical manifestations of HFMD are usually mild and self limiting, a severe EV71 outbreak can lead to a diverse array of neurological diseases. Identification of the specific cellular receptors is crucial for elucidating the mechanism of early virus-host interactions and the pathogenesis of enteroviruses(1). Here we identify human P-selectin glycoprotein ligand-1 (PSGL-1; CD162), a sialomucin membrane protein expressed on leukocytes that has a major role in early stages of inflammation(2-4), as a functional receptor for EV71 using an expression cloning method by panning(5). The N-terminal region of PSGL-1 binds specifically to EV71. Stable PSGL-1 expression allowed EV71 entry and replication, and development of cytopathic effects in nonsusceptible mouse L929 cells. Five out of eight EV71 strains bound soluble PSGL-1 and used intact PSGL-1 as the primary receptor for infection of Jurkat T cells. Three other EV71 strains did not use PSGL-1, suggesting the presence of strain-specific replication of EV71 in leukocytes. EV71 replicated in nonleukocyte cell lines in a PSGL-1-independent manner, indicating the presence of alternative receptor(s) for EV71. The identification of PSGL-1 as a receptor for EV71 sheds new light on a role for PSGL-1-positive leukocytes in cell tropism and pathogenesis during the course of HFMD and other EV71-mediated diseases.