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Two Methods of Heterokaryon Formation to Discover HCV Restriction Factors
Published on: July 16, 2012
Suppression of hepatitis C virus replication by cyclin-dependent kinase inhibitors
Tsubasa Munakata1, Makoto Inada2, Yuko Tokunaga3
1Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan; Department of Microbiology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Abstract:
Hepatitis C virus (HCV) is a causative agent of chronic hepatitis. Although the standard therapy for HCV-infected patients consists of pegylated interferon plus ribavirin, this treatment is associated with serious side effects and high costs, and fails in some patients infected with specific HCV genotypes. To address this problem, we are developing small-molecule inhibitors of cyclin-dependent kinases (CDKs) as novel anti-HCV drug candidates. Previous data showed that HCV replication is inhibited by retinoblastoma protein, which is itself inactivated by CDK-mediated phosphorylation. Here, we report that CDK inhibitors suppress HCV replication in vitro and in vivo, and that CDK4 is required for efficient HCV replication. These findings shed light on the development of novel anti-HCV drugs that target host factors.
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