JC polyomavirus (JCPyV) causes progressive multifocal leukoencephalopathy (PML), a demyelinating disease of the central nervous system, in immunocompromised patients. Although PML used to be rare, recently the incidence of PML has risen due to an increase in immunosuppressive therapy. An in vitro JCPyV infection system could be used for anti-drug screening and investigation of tropism changes, but study of JCPyV in vitro has been limited due to the difficulty of efficiently propagating the virus in cultured cells. PML-type JCPyV efficiently propagates in primary human fetal and progenitor cell–derived astrocytes, but the preparation of cells from human fetuses is associated with severe ethical problems. In this study, human iPS cell–derived astrocytes were exposed to PML-type JCPyV. Infection, replication, and VP1 and T antigens of JCPyV were detected and confirmed in this culture. The non-coding control region (NCCR) of M1-IMRb was conserved in infected cells without point mutations. In addition, PML-type JCPyV genomic DNA in infected cells was detected as a single band of approximately 5.1 kbp, with no deletions. This is the first demonstration that human iPS cell–derived astrocytes efficiently support replication of PML-type JCPyV without production of defective interfering particles. These findings indicated that a culture system using human iPS cell–derived astrocyte would be useful for studies of PML, especially for screening anti-JCPyV drugs.

JC多瘤病毒（JCPyV）在免疫功能低下的患者中引起进行性多灶性白质脑病（PML），这是中枢神经系统的脱髓鞘疾病。尽管PML过去很少见，但最近由于免疫抑制疗法的增加，PML的发病率上升了。一个体外JCPyV感染系统可用于抗药物筛选和取向的变化调查，但JCPyV的研究体外由于难以在培养细胞中有效繁殖该病毒，因此受到限制。PML型JCPyV在人类原代胎儿和祖细胞衍生的星形胶质细胞中有效繁殖，但是从人类胎儿制备细胞会带来严重的伦理问题。在这项研究中，人类iPS细胞衍生的星形胶质细胞暴露于PML型JCPyV。在此培养物中检测并确认了JCPyV的感染，复制以及VP1和T抗原。M1-IMRb的非编码控制区（NCCR）在没有点突变的感染细胞中是保守的。此外，检测到感染细胞中的PML型JCPyV基因组DNA为约5.1 kbp的单条带，无缺失。这是人类iPS细胞来源的星形胶质细胞有效支持PML型JCPyV复制而不会产生有缺陷的干扰颗粒的第一个证明。这些发现表明，使用源自人类iPS细胞的星形胶质细胞的培养系统对PML的研究特别有用，特别是对于筛选抗JCPyV药物。