Chemical genetics approach to hepatitis C virus replication: cyclophilin as a target for anti-hepatitis C virus strategy
Version of Record online: 14 FEB 2007
Copyright © 2007 John Wiley & Sons, Ltd.
Reviews in Medical Virology
Volume 17, Issue 4, pages 245–252, July/August 2007
How to Cite
Watashi, K. and Shimotohno, K. (2007), Chemical genetics approach to hepatitis C virus replication: cyclophilin as a target for anti-hepatitis C virus strategy. Rev. Med. Virol., 17: 245–252. doi: 10.1002/rmv.534
- Issue online: 20 JUN 2007
- Version of Record online: 14 FEB 2007
- Manuscript Accepted: 22 DEC 2006
- Manuscript Received: 21 DEC 2006
- Ministry of Health, Labour and Welfare
- Ministry of Education, Culture, Sports, Science and Technology
- Japanese Society for the Promotion of Science
- Organization for Pharmaceutical Safety
Hepatitis C virus (HCV) is a major causative agent of liver diseases such as chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Because the current standard therapy, interferon (IFN) or pegylated-IFN alone or in combination with ribavirin, is ineffective on approximately half of the HCV-infected patients, alternative therapeutics are greatly needed. The chemical genetics method is a useful strategy to elucidate molecular mechanisms of the viral life cycle and screen for anti-viral agents. This review focuses on the use of chemical genetics approach to virology, which could be called ‘chemical virology’, and introduces an example of such analysis. From a cell culture-based screening, an immunosuppressant cyclosporin A (CsA) was identified as an anti-HCV compound. Analysis using CsA as a bioprobe showed that cyclophilin (CyP) B, a cellular target of CsA, regulates the function of HCV RNA polymerase NS5B, which is essential for efficient viral genome replication. By targeting CyP, HCV genome replication was drastically suppressed. Thus, chemical genetics analysis identified CyPB as a cellular cofactor of HCV genome replication and a target for novel anti-HCV agents. Copyright © 2007 John Wiley & Sons, Ltd.