Inhibitory effect of serotonin antagonists on JC virus propagation in a carrier culture of human neuroblastoma cells

Abstract

Humanpolyomavirus,JCV, causes fataldemyelinating disease, progressivemultifocal leukoencephalopathy (PML). It has been shown that 5HT 2AR acts as a cellular receptor for JCV on human glial cells. In the current study,we examined the inhibitory effects of 5HT 2ARantagonists, ketanserin and ritanserin, both on JCV infection and on propagation by using humanneuroblastomacells IMR-32 and JCI,which continuously produce JCV. Transcriptional analysis revealed that 5HT 2AR 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 5HT 2AR 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. © 2009 The Societies and Blackwell Publishing Asia Pty Ltd.