Biogen IDEC Inc., Cambridge, MA, USA.
J Infect Dis. 2011 Jul 1;204(1):103-14. doi: 10.1093/infdis/jir198.
Progressive multifocal leukoencephalopathy (PML), a fatal demyelinating disease caused by JC virus (JCV) infection of oligodendrocytes, may develop in patients with immune disorders following reactivation of chronic benign infection. Mutations of JCV capsid viral protein 1 (VP1), the capsid protein involved in binding to sialic acid cell receptors, might favor PML onset. Cerebrospinal fluid sequences from 37/40 PML patients contained one of several JCV VP1 amino acid mutations, which were also present in paired plasma but not urine sequences despite the same viral genetic background. VP1-derived virus-like particles (VLPs) carrying these mutations lost hemagglutination ability, showed different ganglioside specificity, and abolished binding to different peripheral cell types compared with wild-type VLPs. However, mutants still bound brain-derived cells, and binding was not affected by sialic acid removal by neuraminidase. JCV VP1 substitutions are acquired intrapatient and might favor JCV brain invasion through abrogation of sialic acid binding with peripheral cells, while maintaining sialic acid-independent binding with brain cells.
进行性多灶性白质脑病（PML）是一种由 JC 病毒（JCV）感染少突胶质细胞引起的致命脱髓鞘疾病，可能在免疫功能紊乱的患者中发生，导致慢性良性感染复发。JCV 衣壳病毒蛋白 1（VP1）的突变，该蛋白参与与唾液酸细胞受体结合，可能有利于 PML 的发生。40 例 PML 患者中有 37 例的脑脊液序列中含有几种 JCV VP1 氨基酸突变，这些突变也存在于配对的血浆中，但不存在于尿液序列中，尽管具有相同的病毒遗传背景。携带这些突变的 VP1 衍生病毒样颗粒（VLPs）丧失了血凝能力，显示出不同的神经节苷脂特异性，并与不同的外周细胞类型的结合能力与野生型 VLPs 相比有所减弱。然而，突变体仍然与脑源性细胞结合，并且结合不受神经氨酸酶去除唾液酸的影响。JCV VP1 取代是在患者体内获得的，可能通过破坏与外周细胞的唾液酸结合，有利于 JCV 对大脑的入侵，同时保持与脑细胞的非依赖唾液酸的结合。
