探讨 NCCR 变异在双报告迷你环上 JC 多瘤病毒表达中的作用。
Exploring the role of NCCR variation on JC polyomavirus expression from dual reporter minicircles.
机构信息
Université Paris Descartes, INSERM Paris, France.
Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Service de Virologie, Paris, France.
出版信息
PLoS One. 2018 Jun 26;13(6):e0199171. doi: 10.1371/journal.pone.0199171. eCollection 2018.
JC virus (JCV), a ubiquitous human polyomavirus, can cause fatal progressive multifocal leukoencephalopathy (PML) in immune compromised patients. The viral genome is composed of two conserved coding regions separated by a highly variable non-coding control region (NCCR). We analyzed the NCCR sequence from 10 PML JCV strains and found new mutations. Remarkably, the NCCR f section was mutated in most cases. We therefore explored the importance of this section in JCV expression in renal (HEK293H) and glioblastoma (U-87MG) cell lines, by adapting the emerging technology of DNA minicircles. Using bidirectional fluorescent reporters, we revealed that impaired NCCR-driven late expression in glioblastoma cells was restored by a short deletion overlapping e and f sections. This study evidenced a relevant link between JCV NCCR polymorphism and cell-type dependent expression. The use of DNA minicircles opens new insights for monitoring the impact of NCCR variation.
JC 病毒（JCV）是一种普遍存在的人类多瘤病毒，可导致免疫功能低下的患者发生致命的进行性多灶性白质脑病（PML）。病毒基因组由两个保守的编码区组成，由高度可变的非编码调控区（NCCR）分隔。我们分析了 10 株 PML JCV 株的 NCCR 序列，发现了新的突变。值得注意的是，NCCR 的 f 区在大多数情况下发生了突变。因此，我们通过适应新兴的 DNA 微环技术，探索了该部分在肾（HEK293H）和神经胶质瘤（U-87MG）细胞系中 JCV 表达的重要性。使用双向荧光报告基因，我们揭示了短缺失重叠 e 和 f 区可恢复神经胶质瘤细胞中 NCCR 驱动的晚期表达受损。这项研究证实了 JCV NCCR 多态性与细胞类型依赖性表达之间存在相关性。DNA 微环的使用为监测 NCCR 变异的影响提供了新的见解。
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