Pharmacological cdk inhibitor R-Roscovitine suppresses JC virus proliferation.
The human Polyomavirus JC virus (JCV) utilizes cellular proteins for viral replication and transcription in the host cell nucleus. These cellular proteins represent potential targets for antiviral drugs against the JCV. In this study, we examined the antiviral effects of the pharmacological cyclin-dependent kinase (cdk) inhibitor R-Roscovitine, which has been shown to have antiviral activity against other viruses. We found that Roscovitine significantly inhibited the viral production and cytopathic effects of the JCV in a JCV-infected cell line. Roscovitine attenuated the transcriptional activity of JCV late genes, but not early genes, and also prevented viral replication via inhibiting phosphorylation of the viral early protein, large T antigen. These data suggest that the JCV requires cdks to transcribe late genes and to replicate its own DNA. That Roscovitine exhibited antiviral activity in JCV-infected cells suggests that Roscovitine might have therapeutic utility in the treatment of progressive multifocal leukoencephalopathy (PML).
Orba
Yasuko
Y
Department of Molecular Pathobiology, Hokkaido University Research Center for Zoonosis Control, N18, W9, Kita-ku, 060-0818, Sapporo, Japan.
Sunden
Yuji
Y
Suzuki
Tadaki
T
Nagashima
Kazuo
K
Kimura
Takashi
T
Tanaka
Shinya
S
Sawa
Hirofumi
H
D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D045744:Cell Line, Tumor; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D006801:Humans; D007577:JC Virus / Q000187:drug effects* / Q000502:physiology; D011687:Purines / Q000494:pharmacology*; D000077546:Roscovitine; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D011687:Purines; D000077546:Roscovitine; D018844:Cyclin-Dependent Kinases