# wombat urls ß PLOS Pathogens: Self-Enhancement of Hepatitis C Virus Replication by Promotion of Specific Sphingolipid Biosynthesis
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Research Article

Self-Enhancement of Hepatitis C Virus Replication by Promotion of Specific Sphingolipid Biosynthesis

  • Yuichi Hirata,

    Affiliation: Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo, Japan

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  • Kazutaka Ikeda,

    Affiliations: Department of Metabolome, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan, Institute for Advanced Biosciences, Keio University, Kakuganji, Tsuruoka, Yamagata, Japan

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  • Masayuki Sudoh,

    Affiliation: Kamakura Research Laboratories, Chugai Pharmaceutical Co., Ltd., Kamakura, Kanagawa, Japan

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  • Yuko Tokunaga,

    Affiliation: Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo, Japan

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  • Akemi Suzuki,

    Affiliation: Institute of Glycoscience, Tokai University, Hiratsuka-shi, Kanagawa, Japan

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  • Leiyun Weng,

    Affiliation: Unit of Viral Genome Regulation, Institut Pasteur of Shanghai, Key Laboratory of Molecular Virology & Immunology, Chinese Academy of Sciences, Shanghai, China

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  • Masatoshi Ohta,

    Affiliation: Institute for Advanced Biosciences, Keio University, Kakuganji, Tsuruoka, Yamagata, Japan

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  • Yoshimi Tobita,

    Affiliation: Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo, Japan

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  • Ken Okano,

    Affiliation: Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., Gotemba, Shizuoka, Japan

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  • Kazuhisa Ozeki,

    Affiliation: Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., Gotemba, Shizuoka, Japan

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  • Kenichi Kawasaki,

    Affiliation: Kamakura Research Laboratories, Chugai Pharmaceutical Co., Ltd., Kamakura, Kanagawa, Japan

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  • Takuo Tsukuda,

    Affiliation: Kamakura Research Laboratories, Chugai Pharmaceutical Co., Ltd., Kamakura, Kanagawa, Japan

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  • Asao Katsume,

    Affiliation: Kamakura Research Laboratories, Chugai Pharmaceutical Co., Ltd., Kamakura, Kanagawa, Japan

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  • Yuko Aoki,

    Affiliation: Kamakura Research Laboratories, Chugai Pharmaceutical Co., Ltd., Kamakura, Kanagawa, Japan

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  • Takuya Umehara,

    Affiliation: Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo, Japan

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  • Satoshi Sekiguchi,

    Affiliation: Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo, Japan

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  • Tetsuya Toyoda,

    Affiliation: Unit of Viral Genome Regulation, Institut Pasteur of Shanghai, Key Laboratory of Molecular Virology & Immunology, Chinese Academy of Sciences, Shanghai, China

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  • Kunitada Shimotohno,

    Affiliation: Research Institute, Chiba Institute of Technology, Narashino, Chiba, Japan

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  • Tomoyoshi Soga,

    Affiliation: Institute for Advanced Biosciences, Keio University, Kakuganji, Tsuruoka, Yamagata, Japan

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  • Masahiro Nishijima,

    Affiliations: National Institute of Health Sciences, Setagaya-ku, Tokyo, Japan, Showa Pharmaceutical University, Machidashi, Tokyo, Japan

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  • Ryo Taguchi,

    Affiliations: Department of Metabolome, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan, Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Kasugai-shi, Aichi, Japan

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  • Michinori Kohara mail

    kohara-mc@igakuken.or.jp

    Affiliation: Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo, Japan

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  • Published: August 16, 2012
  • DOI: 10.1371/journal.ppat.1002860

About the Authors

Yuichi Hirata, Yuko Tokunaga, Yoshimi Tobita, Takuya Umehara, Satoshi Sekiguchi, Michinori Kohara
Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo, Japan
Kazutaka Ikeda, Ryo Taguchi
Department of Metabolome, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
Kazutaka Ikeda, Masatoshi Ohta, Tomoyoshi Soga
Institute for Advanced Biosciences, Keio University, Kakuganji, Tsuruoka, Yamagata, Japan
Masayuki Sudoh, Kenichi Kawasaki, Takuo Tsukuda, Asao Katsume, Yuko Aoki
Kamakura Research Laboratories, Chugai Pharmaceutical Co., Ltd., Kamakura, Kanagawa, Japan
Akemi Suzuki
Institute of Glycoscience, Tokai University, Hiratsuka-shi, Kanagawa, Japan
Leiyun Weng, Tetsuya Toyoda
Unit of Viral Genome Regulation, Institut Pasteur of Shanghai, Key Laboratory of Molecular Virology & Immunology, Chinese Academy of Sciences, Shanghai, China
Ken Okano, Kazuhisa Ozeki
Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., Gotemba, Shizuoka, Japan
Kunitada Shimotohno
Research Institute, Chiba Institute of Technology, Narashino, Chiba, Japan
Masahiro Nishijima
National Institute of Health Sciences, Setagaya-ku, Tokyo, Japan
Masahiro Nishijima
Showa Pharmaceutical University, Machidashi, Tokyo, Japan
Ryo Taguchi
Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Kasugai-shi, Aichi, Japan

Corresponding Author

Email: kohara-mc@igakuken.or.jp

Competing Interests

M. Sudoh, A. Katsume, K. Okano, K. Ozeki, K. Kawasaki, T. Tsukuda, and Y. Aoki are employees of Chugai Pharmaceutical Co. Ltd. This does not alter our adherence to all PLoS Pathogens policies on sharing data and materials.

Author Contributions

Conceived and designed the experiments: M. Kohara. Wrote the paper: Y. Hirata. Y. Hirata performed the experiment of chimeric mice and HCV-infected cells. K. Ikeda, M. Ohta, T. Soga, and R. Taguchi performed lipid analysis by MS spectrometry. M. Sudoh, A. Katsume, and Y. Aoki evaluated the antiviral effects of NA808, K. Okano and K. Ozeki examined the tissue distribution of NA808. K. Kawasaki and T. Tsukuda synthesized derivatives from natural compounds. Y. Tokunaga, Y. Tobita, T. Umehara, and S. Sekiguchi performed some experiments on the chimeric mice. L. Weng and T. Toyoda conducted the experiments on the interaction between RdRp and SM. M. Kohara and Y. Hirata performed data analysis on the chimeric mice and cells. K. Ikeda, M. Ohta, T. Soga, and R. Taguchi performed data analysis on the result of MS spectrometry. A. Suzuki, K. Shimotohno, and M. Nishijima provided tools and expert information.