Involvement of FKBP6 in hepatitis C virus replication

Hirotake Kasai; Kunihiro Kawakami; Hiromasa Yokoe; Kentaro Yoshimura; Masanori Matsuda; Jun Yasumoto; Shinya Maekawa; Atsuya Yamashita; Tomohisa Tanaka; Masanori Ikeda; Nobuyuki Kato; Toru Okamoto; Yoshiharu Matsuura; Naoya Sakamoto; Nobuyuki Enomoto; Sen Takeda; Hideki Fujii; Masayoshi Tsubuki; Masami Kusunoki; Kohji Moriishi

doi:10.1038/srep16699

Involvement of FKBP6 in hepatitis C virus replication

Hirotake Kasai, Kunihiro Kawakami, Hiromasa Yokoe, Kentaro Yoshimura, Masanori Matsuda, Jun Yasumoto, Shinya Maekawa, Atsuya Yamashita, Tomohisa Tanaka, Masanori Ikeda, Nobuyuki Kato, Toru Okamoto, Yoshiharu Matsuura, Naoya Sakamoto, Nobuyuki Enomoto, Sen Takeda, Hideki Fujii, Masayoshi Tsubuki, Masami Kusunoki, Kohji Moriishi

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10 Citations (Scopus)

Abstract

The chaperone system is known to be exploited by viruses for their replication. In the present study, we identified the cochaperone FKBP6 as a host factor required for hepatitis C virus (HCV) replication. FKBP6 is a peptidyl prolyl cis-trans isomerase with three domains of the tetratricopeptide repeat (TPR), but lacks FK-506 binding ability. FKBP6 interacted with HCV nonstructural protein 5A (NS5A) and also formed a complex with FKBP6 itself or FKBP8, which is known to be critical for HCV replication. The Val¹²¹ of NS5A and TPR domains of FKBP6 were responsible for the interaction between NS5A and FKBP6. FKBP6 was colocalized with NS5A, FKBP8, and double-stranded RNA in HCV-infected cells. HCV replication was completely suppressed in FKBP6-knockout hepatoma cell lines, while the expression of FKBP6 restored HCV replication in FKBP6-knockout cells. A treatment with the FKBP8 inhibitor N-(N′, N′-dimethylcarboxamidomethyl)cycloheximide impaired the formation of a homo- or hetero-complex consisting of FKBP6 and/or FKBP8, and suppressed HCV replication. HCV infection promoted the expression of FKBP6, but not that of FKBP8, in cultured cells and human liver tissue. These results indicate that FKBP6 is an HCV-induced host factor that supports viral replication in cooperation with NS5A.

Original language	English
Article number	16699
Journal	Scientific reports
Volume	5
DOIs	https://doi.org/10.1038/srep16699
Publication status	Published - Nov 16 2015

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Kasai, H., Kawakami, K., Yokoe, H., Yoshimura, K., Matsuda, M., Yasumoto, J., Maekawa, S., Yamashita, A., Tanaka, T., Ikeda, M., Kato, N., Okamoto, T., Matsuura, Y., Sakamoto, N., Enomoto, N., Takeda, S., Fujii, H., Tsubuki, M., Kusunoki, M., & Moriishi, K. (2015). Involvement of FKBP6 in hepatitis C virus replication. Scientific reports, 5, [16699]. https://doi.org/10.1038/srep16699

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title = "Involvement of FKBP6 in hepatitis C virus replication",

abstract = "The chaperone system is known to be exploited by viruses for their replication. In the present study, we identified the cochaperone FKBP6 as a host factor required for hepatitis C virus (HCV) replication. FKBP6 is a peptidyl prolyl cis-trans isomerase with three domains of the tetratricopeptide repeat (TPR), but lacks FK-506 binding ability. FKBP6 interacted with HCV nonstructural protein 5A (NS5A) and also formed a complex with FKBP6 itself or FKBP8, which is known to be critical for HCV replication. The Val121 of NS5A and TPR domains of FKBP6 were responsible for the interaction between NS5A and FKBP6. FKBP6 was colocalized with NS5A, FKBP8, and double-stranded RNA in HCV-infected cells. HCV replication was completely suppressed in FKBP6-knockout hepatoma cell lines, while the expression of FKBP6 restored HCV replication in FKBP6-knockout cells. A treatment with the FKBP8 inhibitor N-(N′, N′-dimethylcarboxamidomethyl)cycloheximide impaired the formation of a homo- or hetero-complex consisting of FKBP6 and/or FKBP8, and suppressed HCV replication. HCV infection promoted the expression of FKBP6, but not that of FKBP8, in cultured cells and human liver tissue. These results indicate that FKBP6 is an HCV-induced host factor that supports viral replication in cooperation with NS5A.",

author = "Hirotake Kasai and Kunihiro Kawakami and Hiromasa Yokoe and Kentaro Yoshimura and Masanori Matsuda and Jun Yasumoto and Shinya Maekawa and Atsuya Yamashita and Tomohisa Tanaka and Masanori Ikeda and Nobuyuki Kato and Toru Okamoto and Yoshiharu Matsuura and Naoya Sakamoto and Nobuyuki Enomoto and Sen Takeda and Hideki Fujii and Masayoshi Tsubuki and Masami Kusunoki and Kohji Moriishi",

note = "Funding Information: We thank C. E. Cameron, T. Wakita, F. Edlich, and G. Fisher for providing plasmids. We also thank M. Furugori for her secretarial work and C. Endoh for technical assistance. This work was supported by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science, and Technology (15K08493); the Ministry of Health, Labor, and Welfare, Japan (H24-Kanen-008); and the Japan Agency for Medical Research and Development (H25-Kanen-002 and −008). Publisher Copyright: {\textcopyright} 2015, Nature Publishing Group. All rights reserved.",

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AU - Kawakami, Kunihiro

AU - Yokoe, Hiromasa

AU - Yoshimura, Kentaro

AU - Matsuda, Masanori

AU - Yasumoto, Jun

AU - Maekawa, Shinya

AU - Yamashita, Atsuya

AU - Tanaka, Tomohisa

AU - Ikeda, Masanori

AU - Kato, Nobuyuki

AU - Okamoto, Toru

AU - Matsuura, Yoshiharu

AU - Sakamoto, Naoya

AU - Enomoto, Nobuyuki

AU - Takeda, Sen

AU - Fujii, Hideki

AU - Tsubuki, Masayoshi

AU - Kusunoki, Masami

AU - Moriishi, Kohji

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PY - 2015/11/16

Y1 - 2015/11/16

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Involvement of FKBP6 in hepatitis C virus replication

Abstract

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