Infectious Entry and Neutralization of Pathogenic JC Polyomaviruses
Infectious Entry and Neutralization of Pathogenic JC Polyomaviruses
复制标题
DOI：
10.1016/j.celrep.2017.10.027
复制
发表时间：
2017-10-31
期刊：
影响因子：
8.8
通讯作者：
Buck, Christopher B.
中科院分区：
文献类型：
--
作者：
Geoghegan, Eileen M.;Pastrana, Diana V.;Buck, Christopher B.
进行性多灶性白质脑病（PML）是一种由JC多瘤病毒（JCV）不受控制的复制引起的致死性脑病。从PML患者脑中回收的JCV菌株携带阻止唾液酸化聚糖参与的突变，唾液酸化聚糖被认为是野生型JCV感染性进入的受体。在这份报告中，我们表明，非唾液酸化的糖胺聚糖（GAG）可以作为替代附件受体的感染性进入野生型和PML突变型JCV菌株。在GAG介导的附着后，PML突变株与非唾液酸化的非GAG共受体聚糖（如无唾液酸-GM 1）结合。从从PML恢复的患者中分离的JCV中和单克隆抗体似乎通过阻止JCV主要衣壳蛋白的顶袋中的附着后共受体聚糖的对接来阻断感染。GAG依赖性/唾液酸化聚糖非依赖性替代进入途径的鉴定应有助于开发感染抑制剂，包括重组中和抗体。
Progressive multifocal leukoencephalopathy (PML) is a lethal brain disease caused by uncontrolled replication of JC polyomavirus (JCV). JCV strains recovered from the brains of PML patients carry mutations that prevent the engagement of sialylated glycans, which are thought to serve as receptors for the infectious entry of wild-type JCV. In this report, we show that non-sialylated glycosaminoglycans (GAGs) can serve as alternative attachment receptors for the infectious entry of both wild-type and PML mutant JCV strains. After GAG-mediated attachment, PML mutant strains engage non-sialylated non-GAG co-receptor glycans, such as asialo-GM1. JCV-neutralizing monoclonal antibodies isolated from patients who recovered from PML appear to block infection by preventing the docking of post-attachment co-receptor glycans in an apical pocket of the JCV major capsid protein. Identification of the GAG-dependent/sialylated glycan-independent alternative entry pathway should facilitate the development of infection inhibitors, including recombinant neutralizing antibodies.