Pharmacological cdk inhibitor R-Roscovitine suppresses JC virus proliferation

Journal Article · Sat Jan 05 04:00:00 EST 2008 · Virology

DOI:https://doi.org/10.1016/j.virol.2007.08.034· OSTI ID:21078008

Orba, Yasuko ^[1]; Sunden, Yuji ^[2]; Suzuki, Tadaki ^[1]; Nagashima, Kazuo ^[3]; Kimura, Takashi ^[1]; Tanaka, Shinya ^[3]; Sawa, Hirofumi ^[1]

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1. Department of Molecular Pathobiology, Hokkaido University Research Center for Zoonosis Control, N18, W9, Kita-ku, 060-0818, Sapporo (Japan)
2. Laboratory of Comparative Pathology, Hokkaido University Graduate School of Veterinary Medicine, N18, W9, Kita-ku, 060-0818, Sapporo (Japan)
3. Laboratory of Molecular and Cellular Pathology, Hokkaido University Graduate School of Medicine, N15, W7, Kita-ku, 060-8638, Sapporo (Japan)

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)

• OSTI ID: 21078008
• Journal Information: Virology, Journal Name: Virology Journal Issue: 1 Vol. 370; ISSN VIRLAX; ISSN 0042-6822
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANTIGENS
CELL NUCLEI
CELL PROLIFERATION
DNA
DRUGS
GENES
PHOSPHORYLATION
PROTEINS
TRANSCRIPTION
VIRUSES