Interferon beta1-a and selective anti-5HT(2a) 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 (IFNbeta1-a) and Tysabri (Natalizumab) and the recent reports linking JCV infection to the 5HT(2a) serotonin receptor led us to evaluate the effects of IFNbeta1-a and a panel of 5HT(2a) receptor antagonists for their ability to modulate virus infection. IFNbeta1-a was found to be a potent inhibitor of both virus infection and viral early and late gene expression. In addition, several 5HT(2a) receptor antagonists inhibited initial infection of cells by JCV but were less effective at reducing viral loads in an already established infection.
O'Hara
B A
BA
Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI 02912, USA.
Atwood
W J
WJ
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D002450:Cell Communication / Q000187:drug effects; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D017930:Genes, Reporter; D006801:Humans; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000494:pharmacology* / Q000627:therapeutic use; D007577:JC Virus / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology; D007968:Leukoencephalopathy, Progressive Multifocal / Q000188:drug therapy / Q000821:virology*; D000069442:Natalizumab; D009457:Neuroglia / Q000187:drug effects / Q000821:virology*; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D019562:Viral Load
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000069442:Natalizumab; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D016899:Interferon-beta; D000068556:Interferon beta-1a