Inhibitory effect of serotonin antagonists on JC virus propagation in a carrier culture of human neuroblastoma cells.
Human polyomavirus, JCV, causes fatal demyelinating disease, progressive multifocal leukoencephalopathy (PML). It has been shown that 5HT(2A)R acts as a cellular receptor for JCV on human glial cells. In the current study, we examined the inhibitory effects of 5HT(2A)R 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 5HT(2A)R was constitutively expressed in JCI cells. Treatments with 5HT(2A)R 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 5HT(2A)R antagonists. These results indicate that 5HT(2A)R 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.
Nukuzuma
Souichi
S
Department of Microbiology, Kobe Institute of Health, Kobe, Hyogo, Japan. s-nuku@gj8.so-net.ne.jp
Nakamichi
Kazuo
K
Nukuzuma
Chiyoko
C
Takegami
Tsutomu
T
D045744:Cell Line, Tumor; D015536:Down-Regulation; D006801:Humans; D007577:JC Virus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development*; D007650:Ketanserin / Q000494:pharmacology; D009447:Neuroblastoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics / Q000378:metabolism; D016713:Ritanserin / Q000494:pharmacology; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology*; D014776:Virus Cultivation; D014779:Virus Replication / Q000187:drug effects
D044402:Receptor, Serotonin, 5-HT2A; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists; D016713:Ritanserin; D007650:Ketanserin