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HCV genotype 1b chimeric replicon with NS5B of JFH-1 exhibited resistance to cyclosporine A

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Abstract

Cyclosporine A (CsA) is a well-characterized anti-HCV reagent. Recently it was reported that the genotype 2a JFH-1 strain was more resistant than genotype 1 HCV strains to CsA in a cell culture system. However, the JFH-1 responsible region for the resistance to CsA remains unclear. It was also demonstrated that in genotype 1b HCVs, NS5B interacts with cyclophilin (CyP). To clarify whether or not NS5B of JFH-1 is significant for CsA resistance, we developed a chimeric replicon with NS5B of JFH-1 in the genotype 1b backbone. The chimeric replicon was more resistant to CsA than the parental genotype 1b replicon. Furthermore, reduction of CyPA had a greater effect on HCV RNA replication and sensitivity to CsA than reduction of CyPB. Here, we demonstrated that NS5B of JFH-1 contributed to this strain’s CsA-resistant phenotype. NS5B and CyPA are significant for determining HCV’s sensitivity to CsA.

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Acknowledgments

We thank Dr. Trono for the VSV-G-pseudotyped HIV-1-based vector system pCMVΔR8.91, pMDG2, pSUPER, and pRDI292. We also thank A. Morishita and T. Nakamura for their technical assistance. This work was supported by a grant-in-aid for the third-term comprehensive 10-year strategy for cancer control and by a grant-in-aid for research on hepatitis, both from the Ministry of Health, Labor and Welfare of Japan. K. A. was supported by a Research Fellowship from the Japan Society for the Promotion of Science for Young Scientists.

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Authors and Affiliations

  1. Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama, 700-7558, Japan

    Ken-ichi Abe, Masanori Ikeda, Yasuo Ariumi, Hiromichi Dansako & Nobuyuki Kato

  2. Department of Virology II, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo, 162-8640, Japan

    Takaji Wakita

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  1. Ken-ichi Abe
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  2. Masanori Ikeda
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  3. Yasuo Ariumi
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  4. Hiromichi Dansako
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  5. Takaji Wakita
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  6. Nobuyuki Kato
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Correspondence to Masanori Ikeda.

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Abe, Ki., Ikeda, M., Ariumi, Y. et al. HCV genotype 1b chimeric replicon with NS5B of JFH-1 exhibited resistance to cyclosporine A. Arch Virol 154, 1671–1677 (2009). https://doi.org/10.1007/s00705-009-0502-x

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  • DOI: https://doi.org/10.1007/s00705-009-0502-x

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