Interferon β1-a and selective anti-5HT2a receptor antagonists inhibit infection of human glial cells by JC virus

JC virus (JCV) is the causative agent of progressive multifocal leukoenchaphalopathy (PML). The disease develops when JCV gains access to the central nervous system, infects and destroys oligodendrocytes. The disease is rapidly progressing, typically fatal and no effective therapies exist to treat or prevent PML. The recent occurrence of PML in multiple sclerosis patients being treated with Avonex (IFNβ1-a) and Tysabri (Natalizumab) and the recent reports linking JCV infection to the 5HT2a serotonin receptor led us to evaluate the effects of IFNβ1-a and a panel of 5HT2a receptor antagonists for their ability to modulate virus infection. IFNβ1-a was found to be a potent inhibitor of both virus infection and viral early and late gene expression. In addition, several 5HT2a receptor antagonists inhibited initial infection of cells by JCV but were less effective at reducing viral loads in an already established infection.