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Journal of Virology, May 2006, p. 4510-4520, Vol. 80, No. 9
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.9.4510-4520.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Diverse Effects of Cyclosporine on Hepatitis C Virus Strain Replication

Naoto Ishii,1,{dagger} Koichi Watashi,1,{dagger} Takayuki Hishiki,1 Kaku Goto,1 Daisuke Inoue,1 Makoto Hijikata,1 Takaji Wakita,2 Nobuyuki Kato,3 and Kunitada Shimotohno1*

Laboratory of Human Tumor Viruses, Department of Viral Oncology, Institute for Virus Research, Kyoto University, Kyoto,1 Department of Microbiology, Tokyo Metropolitan Institute for Neuroscience, Tokyo,2 Department of Molecular Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan3

Received 18 December 2005/ Accepted 10 February 2006

Recently, a production system for infectious particles of hepatitis C virus (HCV) utilizing the genotype 2a JFH1 strain has been developed. This strain has a high capacity for replication in the cells. Cyclosporine (CsA) has a suppressive effect on HCV replication. In this report, we characterize the anti-HCV effect of CsA. We observe that the presence of viral structural proteins does not influence the anti-HCV activity of CsA. Among HCV strains, the replication of genotype 1b replicons was strongly suppressed by treatment with CsA. In contrast, JFH1 replication was less sensitive to CsA and its analog, NIM811. Replication of JFH1 did not require the cellular replication cofactor, cyclophilin B (CyPB). CyPB stimulated the RNA binding activity of NS5B in the genotype 1b replicon but not the genotype 2a JFH1 strain. These findings provide an insight into the mechanisms of diversity governing virus-cell interactions and in the sensitivity of these strains to antiviral agents.

* Corresponding author. Mailing address: Laboratory of Human Tumor Viruses, Department of Viral Oncology, Institute for Virus Research, Kyoto University, 53 Kawaharacho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan. Phone: 81-75-751-4000. Fax: 81-75-751-3998. E-mail: kshimoto{at}virus.kyoto-u.ac.jp.

{dagger} N.I. and K.W. contributed equally to this work.

Journal of Virology, May 2006, p. 4510-4520, Vol. 80, No. 9
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.9.4510-4520.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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