Inhibitory effect of serotonin antagonists on JC virus propagation in a carrier culture of human neuroblastoma cells
Inhibitory effect of serotonin antagonists on JC virus propagation in a carrier culture of human neuroblastoma cells
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血清素拮抗剂对人神经母细胞瘤细胞载体培养物中 JC 病毒传播的抑制作用
DOI：
10.1111/j.1348-0421.2009.00156.x
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发表时间：
2009
影响因子：
2.6
通讯作者：
T. Takegami
中科院分区：
文献类型：
--
作者：
S. Nukuzuma;K. Nakamichi;C. Nukuzuma;T. Takegami
人多瘤病毒，JCV，导致致命的脱髓鞘疾病，进行性多灶性白质脑病（PML）。已显示5 HT 2AR作为JCV在人神经胶质细胞上的细胞受体。在当前的研究中，我们使用持续产生JCV的人神经母细胞瘤细胞IMR-32和JCI检查了5 HT 2AR拮抗剂酮色林和利坦色林对JCV感染和增殖的抑制作用。转录分析显示，5-HT 2AR在JCI细胞中组成型表达。用5 HT 2AR拮抗剂处理导致子代病毒的滴度和感染的JCI细胞的群体显著降低。此外，在5 HT 2AR拮抗剂存在下，JCI细胞中JCV基因组DNA的量减少。这些结果表明，5 HT 2AR拮抗剂对JCV感染和繁殖具有抑制作用，JCI细胞适用于抗JCV的抗病毒剂的药理学评价的实验模型。
Human polyomavirus, JCV, causes fatal demyelinating disease, progressive multifocal leukoencephalopathy (PML). It has been shown that 5HT2AR acts as a cellular receptor for JCV on human glial cells. In the current study, we examined the inhibitory effects of 5HT2AR antagonists, ketanserin and ritanserin, both on JCV infection and on propagation by using human neuroblastoma cells IMR‐32 and JCI, which continuously produce JCV. Transcriptional analysis revealed that 5HT2AR was constitutively expressed in JCI cells. Treatments with 5HT2AR antagonists led to a significant reduction in the titers of progeny viruses and the population of infected JCI cells. In addition, the amount of JCV genomic DNA was decreased in JCI cells in the presence of 5HT2AR antagonists. These results indicate that 5HT2AR antagonists have an inhibitory effect on JCV infection and reproduction, and JCI cells are applicable to an experimental model for pharmacological evaluation of antiviral agents against JCV.