CX3CR1 is an important surface molecule for respiratory syncytial virus infection in human airway epithelial cells
CX3CR1 is an important surface molecule for respiratory syncytial virus infection in human airway epithelial cells
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DOI：
10.1099/vir.0.000218
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发表时间：
2015-09-01
影响因子：
3.8
通讯作者：
Anderson, Larry J.
中科院分区：
文献类型：
--
作者：
Chirkova, Tatiana;Lin, Songbai;Anderson, Larry J.
呼吸道合胞病毒（RSV）是婴幼儿严重肺炎和细支气管炎的主要病因，并导致终生疾病。了解感染的生物学，包括病毒与细胞表面的结合，应该有助于开发抗病毒药物或疫苗。RSV F和G糖蛋白通过肝素结合结构域结合细胞表面硫酸肝素蛋白聚糖（HSPG）。G蛋白还具有CX 3C趋化因子基序，其结合到Fractalkine受体CX 3CR 1。G蛋白与CX 3CR 1的结合对于永生化细胞系的感染并不重要，但据报道对于人感染的主要部位-原代人气道上皮细胞（HAEC）是如此。我们研究了CX 3CR 1在RSV感染中的作用，使用CX 3CR 1转染的细胞系和具有可变百分比的CX 3CR 1表达细胞的HAEC，以及抗CX 3CR 1抗体或RSV CX 3C基序突变的影响。缺乏HSPGs的永生化细胞具有低RSV结合和感染，CX 3CR 1转染显著增加。CX 3CR 1主要在纤毛细胞上表达，并且类似于HAECs中50%的RSV感染细胞是CX 3CR 1（+）。具有更多CX 3CR 1表达细胞的HAEC在RSV感染中成比例增加。用抗CX 3CR 1抗体或CX 3C基序突变阻断G与CX 3CR 1的结合显著降低HAEC中的RSV感染。细胞因子产生的动力学表明，RSV/CX 3CR 1相互作用诱导RANTES（调节活化正常T细胞表达和分泌的蛋白）、IL-8和fractalkine产生，同时其下调IL-15、IL 1-RA和单核细胞趋化蛋白-1。因此，RSV G蛋白/CX 3CR 1相互作用可能在感染和感染诱导的气道上皮（人类感染的主要部位）反应中很重要。
Respiratory syncytial virus (RSV) is a major cause of severe pneumonia and bronchiolitis in infants and young children, and causes disease throughout life. Understanding the biology of infection, including virus binding to the cell surface, should help develop antiviral drugs or vaccines. The RSV F and G glycoproteins bind cell surface heparin sulfate proteoglycans (HSPGs) through heparin-binding domains. The G protein also has a CX3C chemokine motif which binds to the fractalkine receptor CX3CR1. G protein binding to CX3CR1 is not important for infection of immortalized cell lines, but reportedly is so for primary human airway epithelial cells (HAECs), the primary site for human infection. We studied the role of CX3CR1 in RSV infection with CX3CR1-transfected cell lines and HAECs with variable percentages of CX3CR1-expressing cells, and the effect of anti-CX3CR1 antibodies or a mutation in the RSV CX3C motif. Immortalized cells lacking HSPGs had low RSV binding and infection, which was increased markedly by CX3CR1 transfection. CX3CR1 was expressed primarily on ciliated cells, and similar to 50 % of RSV-infected cells in HAECs were CX3CR1(+). HAECs with more CX3CR1-expressing cells had a proportional increase in RSV infection. Blocking G binding to CX3CR1 with anti-CX3CR1 antibody or a mutation in the CX3C motif significantly decreased RSV infection in HAECs. The kinetics of cytokine production suggested that the RSV/CX3CR1 interaction induced RANTES (regulated on activation normal T-cell expressed and secreted protein), IL-8 and fractalkine production, whilst it downregulated IL-15, IL1-RA and monocyte chemotactic protein-1. Thus, the RSV G protein/CX3CR1 interaction is likely important in infection and infection-induced responses of the airway epithelium, the primary site of human infection.