Direct binding of respiratory syncytial virus to pneumococci: A phenomenon that enhances both pneumococcal adherence to human epithelial cells and pneumococcal invasiveness in a murine model
Direct binding of respiratory syncytial virus to pneumococci: A phenomenon that enhances both pneumococcal adherence to human epithelial cells and pneumococcal invasiveness in a murine model
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DOI：
10.1203/01.pdr.0000188699.55279.1b
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发表时间：
2005-12-01
影响因子：
3.6
通讯作者：
Wolfs, TFW
中科院分区：
文献类型：
--
作者：
Hament, JM;Aerts, PC;Wolfs, TFW
在以前的研究中，我们发现肺炎球菌粘附上皮细胞增强了先前的呼吸道合胞病毒（RSV）感染。RSV-糖蛋白，表达在感染的细胞表面，可能在这种增强的肺炎球菌结合中发挥作用，作为细菌受体。在当前的研究中，试图分析肺炎球菌与RSV病毒粒子直接相互作用的能力。通过流式细胞术，可以检测到RSV和肺炎球菌之间的直接相互作用。肝素，一种与RSV蛋白G相互作用的RSV感染性抑制剂，阻断了RSV-肺炎球菌结合，表明后者的相互作用确实是由蛋白G介导的。RSV-肺炎球菌复合物表现出增强的粘附未感染的人上皮细胞，与肺炎球菌粘附没有绑定RSV相比，这种增强也被肝素阻断。此外，在小鼠模型中体内探索了这些体外发现的意义。在肺炎球菌攻击前第4天用RSV预处理的小鼠和同时用两种试剂感染的小鼠均显示出比对照组显著更高的菌血症水平。同时感染这两种药物最强烈地增强了肺炎球菌菌血症的发展。假设直接病毒结合是RSV可诱导肺炎球菌与上皮细胞结合增强的另一种机制，当与RSV同时给予小鼠时，这种现象在体内转化为肺炎球菌的更高侵袭性。显然，RSV在此过程中作为细菌和未感染上皮细胞之间的直接偶联颗粒，从而增加肺炎球菌的定植并增强其侵袭力。
In a previous study we showed that pneumococcal adherence to epithelial cells was enhanced by a preceding respiratory syncytial virus (RSV) infection. RSV-glycoproteins, expressed on the infected cell surface, may play a role in this enhanced pneumococcal binding, by acting as bacterial receptors. In the current study, it was attempted to analyze the capacity of pneumococci to interact directly with RSV virions. By flow-cytometry, a direct interaction between RSV and pneumococci could be detected. Heparin, an inhibitor of RSV infectivity that interacts with RSV protein-G, blocked RSV-pneumococcal binding, indicating that the latter interaction is indeed mediated by protein-G. RSV-pneumococcal complexes showed enhanced adherence to uninfected human epithelial cells, compared with pneumococcal adherence without bound RSV, and this enhancement was also blocked by heparin. In addition, the significance of these findings in vitro was explored in vivo in a murine model. Both mice that were pretreated with RSV at day 4 before pneumococcal challenge and mice infected with both agents simultaneously showed significantly higher levels of bacteraemia than controls. Simultaneous infection with both agents enhanced the development of pneumococcal bacteraemia most strongly. It was hypothesized that direct viral binding is another mechanism by which RSV can induce enhanced pneumococcal binding to epithelial cells, a phenomenon that is translated in vivo by a higher invasiveness of pneumococci when administered simultaneously with RSV to mice. Apparently, RSV acts in this process as a direct coupling particle between bacteria and uninfected epithelial cells, thereby increasing colonization by and enhancing invasiveness of pneumococci.