Human iPS cell-derived astrocytes support efficient replication of progressive multifocal leukoencephalopathy-type JC polyomavirus
Human iPS cell-derived astrocytes support efficient replication of progressive multifocal leukoencephalopathy-type JC polyomavirus
复制标题
人 iPS 细胞衍生的星形胶质细胞支持进行性多灶性白质脑病型 JC 多瘤病毒的有效复制
DOI：
10.1016/j.bbrc.2020.09.117
复制
发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Yoh-ichi Tagawa
中科院分区：
文献类型：
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作者：
Emiko Shimbo;Souichi Nukuzuma;Yoh-ichi Tagawa
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)，这是一种中枢神经系统脱髓鞘疾病。虽然PML过去很少见，但最近由于免疫抑制治疗的增加，PML的发病率有所上升。JCPyV体外感染系统可用于药物筛选和嗜性变化的研究，但由于JCPyVin病毒在培养细胞中难以有效繁殖，其体外研究一直受到限制。PML型JCPyV在原代人类胎儿和祖细胞来源的星形胶质细胞中有效繁殖，但从人类胎儿中制备细胞与严重的伦理问题有关。在这项研究中，人的iPS细胞来源的星形胶质细胞暴露于PML类型的JCPyV。在该培养物中检测到JCPyV的感染、复制以及VP1和T抗原，并进行了确认。M1-IMRB的非编码控制区(NCCR)在无点突变的感染细胞中是保守的。此外，在感染细胞中检测到的PML型JCPyV基因组DNA是一条约5.1kbp的单一条带，没有缺失。这是首次证明人类iPS细胞来源的星形胶质细胞有效地支持PML型JCPyV的复制，而不产生有缺陷的干扰颗粒。这些发现表明，使用人iPS细胞来源的星形胶质细胞的培养系统将有助于PML的研究，特别是在筛选抗JCPyV药物方面。
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. Anin vitroJCPyV infection system could be used for anti-drug screening and investigation of tropism changes, but study of JCPyVin vitrohas 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.