Basic research on persistent infection of HCV and molecular mechanisms of RNA interference

• Project/Area Number: 23590555
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Virology
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: KASAI MASATAKA 国立感染症研究所, 免疫部, 研究員 (10142134)
• Co-Investigator(Kenkyū-buntansha): 深澤 征義 国立感染症研究所, 細胞化学部 (20291130)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: HCV持続感染 / RNA干渉 / TRAX / Translin / Translinタンパク質 / TRAXタンパク質

Research Abstract

TRAX (Translin-associated factor X) is known as a component of RISC (RNA-induced silencing complex) that is involved in RNA interference (RNAi). Given the significant role of TRAX on RNAi machinery, we analyzed its effect on the mechanism of persistent infection of hepatitis C virus (HCV). Although we could not prove the involvement of TRAX in HCV infection during the study period, we obtained the following results for the nature of TRAX molecule: 1)TRAX protein alone cannot be cellularly expressed. 2)TRAX protein usually exists as a complex with Translin protein to escape from ubiquitin-independent proteasome degradation pathway 3) The C-terminal region of TRAX protein is susceptible to degradation.

Research Products

• [Journal Article] Retinoids and rexinoids inhibit hepatitis C virus independently of retinoid receptor signaling (2014)
  • Author(s): Murakami Y, Fukasawa M, Kaneko Y, Suzuki T, Wakita T, and Fukazawa H.
  • Journal Title: Microbes and Infection Volume: 16 Pages: 114-122
• [Journal Article] Prominent Steatosis with Hypermetabolism of the Cell Line Permissive for Years of Infection with Hepatitis C Virus (2014)
  • Author(s): Sugiyama K, Ebinuma H, Nakamoto N, Sakasegawa N, Murakami Y, Chu P-S, Usui S, Ishibashi Y, Wakayama Y, Taniki N, Murata H, Saito Y, Fukasawa M, Saito K, Yamagishi Y, Wakita T, Takaku H, Hibi T, Saito H, Kanai T
  • Journal Title: PLOS ONE Volume: 9(4)
• [Journal Article] Retinoids and rexinoids inhibit hepatitis C virus independently of retinoid receptor signaling (2014)
  • Author(s): Yuko Murakami, Masayoshi Fukasawa, Yukihiro Kaneko, Tetsuro Suzuki, TakajiWakita, Hidesuke Fukazawa
  • Journal Title: Microbes and Infection Volume: 16(2) Pages: 114-122
  • Peer Reviewed
• [Journal Article] Prominent Steatosis with Hypermetabolism of the Cell Line Permissive for Years of Infection with Hepatitis C Virus (2014)
  • Author(s): Kazuo Sugiyama, HirotoshiEbinuma, Nobuhiro Nakamoto, Noriko Sakasegawa, Yuko Murakami, Po-sung Chu, Shingo Usui, Yuka Ishibashi, Yuko Wakayama, NobuhitoTaniki, Hiroko Murata, Yoshimasa Saito, Masayoshi Fukasawa et al.
  • Journal Title: PLOS ONE Volume: 9(4) e94460 Pages: 1-18
  • Peer Reviewed
• [Journal Article] RP58 regulates the multipolar-bipolar transition of newborn neurons in the developing cerebral cortex (2013)
  • Author(s): Ohtaka-Maruyama C, Hirai, S., Miwa, A., Heng, JI., Shitara, H., Ishii, R., Taya, C., Kawano, H., Kasai, M., Nakajima, K., and Okado, H.
  • Journal Title: Cell Reports Volume: 21 Pages: 458-471
• [Journal Article] Selective estrogen receptor modulators inhibit hepatitis C virus infection at multiple steps of the virus life cycle (2013)
  • Author(s): Murakami Y, Fukasawa M, Kaneko Y, Suzuki T, Wakita T, and Fukazawa H.
  • Journal Title: Microbes and Infection Volume: 15 Pages: 45-55
• [Journal Article] A class II phosphoinositide 3-kinase plays an indispensable role in hepatitis C virus replication (2013)
  • Author(s): Maehama T, Fukasawa M, Date T, Wakita T, Hanada K.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 440(1) Pages: 150-156
• [Journal Article] A class II phosphoinositide 3-kinase plays an indispensable role in hepatitis C virus replication (2013)
  • Author(s): Maehama T, Fukasawa M, Date T, Wakita T, Hanada K.
  • Journal Title: Biochem.Biophys. Res.Commun. Volume: 440(1) Pages: 150-156
  • Peer Reviewed
• [Journal Article] Selective estrogen receptor modulators inhibit hepatitis C virus infection at multiple steps of thevirus lifecycle (2013)
  • Author(s): Y. Murakami, M. Fukasawa, Y. Kaneko, T. Suzuki, T. Wakita, and H. Fukazawa
  • Journal Title: Microbes and Infection Volume: 15 Pages: 45-55
  • Peer Reviewed
• [Journal Article] Translin/TRAX deficiency affects mesenchymal differentiation programs and induces bone marrow failure (2012)
  • Author(s): Ishida, R., Aoki, K., Nakahara, K., Fukuda, Y., Ohhori, M., Saito, Y., Kano, K., Matsuda, J., Asano, S., Maziarz, RT., and Kasai, M.
  • Journal Title: Stem Cells and Human Diseases Volume: Chapter 21 Pages: 468-476
• [Journal Article] RP58 controls neuron and astrocyte differentiation by downregulating the expression of Id1-4 genes in the developing cortex (2012)
  • Author(s): Hirai, S., Miwa, A., Ohtaka-Maruyama C, Kasai, M., Okabe, S., Hata, Y., and Okado, H.
  • Journal Title: EMBO J. Volume: 31 Pages: 1190-1202
• [Journal Article] RP58 controls neuron and astrocyte differentiation by downregulating the expression of Id1-4 genes in the developing cortex. (2012)
  • Author(s): Hirai S, Miwa A, Ohtaka-Maruyama C, Kasai M, Okabe S, Hata Y, Okado H.
  • Journal Title: EMBO J. Volume: 31 Pages: 1190-1202
  • Peer Reviewed
• [Journal Article] Translin/TRAX deficiency affects mesenchymal differentiation programs and induces bone marrow failure (2012)
  • Author(s): Ishida R, Aoki K, Nakahara K, Fukuda Y, Ohhori M, Saito Y, Kano K, Matsuda J, Asano S, Maziarz RT, Kasai M
  • Journal Title: Stem Cells and Human Diseases, Springer-Verlag Volume: Chapter 21 Pages: 467-484
• [Presentation] TRAXはユビキチン非依存的なプロテアソーム分解を受ける (2014)
  • Author(s): 白砂圭崇、葛西正孝、花田賢太郎、安部良、深澤征義
  • Organizer: 日本薬学会第134年会
  • Place of Presentation: 熊本
• [Presentation] TRAXはユビキチン非依存的なプロテアソーム分解を受ける (2014)
  • Author(s): 白砂圭崇、葛西正孝、花田賢太郎、安部良、深澤征義
  • Organizer: 日本薬学会第１３４年会
  • Place of Presentation: 熊本
• [Presentation] The role of Translin/TRAX complex in mesenchymal differentiation programs (2013)
  • Author(s): Kasai, M., Ishida, R., Strominger, JL., and Asano, S.
  • Organizer: AsiaCORD2013: New Perspectives in Mesenchymal Stem Cell Research
  • Place of Presentation: 神戸
  • Invited
• [Presentation] C型肝炎ウイルスへの感染感受性を欠損した宿主肝細胞変異株の分離と性状解析 (2013)
  • Author(s): 白砂圭崇、鈴木哲朗、脇田隆字、花田賢太郎、安部良、深澤征義
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: 横浜
• [Presentation] HCV感染におけるVimentinの細胞内分布変化 (2013)
  • Author(s): 谷田以誠、深澤征義、脇田隆字、花田賢太郎
  • Organizer: 第61回日本ウイルス学会学術集会
  • Place of Presentation: 神戸
• [Presentation] ヒトTRAX蛋白質の発現量の制御 (2012)
  • Author(s): 白砂圭崇、穴井凉、花田賢太郎、葛西正孝、深澤征義
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 北海道
  • Year and Date: 2012-03-29
• [Presentation] Isolation and characterization of a mutant hepatitis C virus adapted to mouse CD81 (2012)
  • Author(s): Masayoshi Fukasawa, Ryo Anai, Yoshitaka Shirasago, Kyoko Saito, Yuko Murakami, Hidesuke Fukazawa, Tetsuro Suzuki, Takaji Wakita, Jo Chiba, Kentaro Hanada
  • Organizer: The 19th International Symposium on Hepatitis C Virus and Related Viruses
  • Place of Presentation: Italy
• [Presentation] 高感染能を有するHCV JFH-1適応変異株の性状解析 (2012)
  • Author(s): 白砂圭崇、齋藤恭子、村上裕子、深澤秀輔、鈴木哲朗、脇田隆字、花田賢太郎、千葉丈、安部良、深澤征義
  • Organizer: 第60回日本ウイルス学会学術集会
  • Place of Presentation: 大阪
• [Presentation] In vitro and in vivo inhibition of hepatitis C virus infection by mouse anti-human claudin 1 monoclonal antibodies (2012)
  • Author(s): Masayoshi Fukasawa, Shotaro Nagase, Mayo Yamashita, Kentaro Hanada, Akihiro Watari, Kiyohito Yagi, Masuo Kondoh
  • Organizer: The 2013 ASCB Annual Meeting
  • Place of Presentation: New Orleans, USA
• [Presentation] Isolation and characterization of a mutant hepatitis C virus adapted to mouse CD81 (2012)
  • Author(s): Masayoshi Fukasawa, Ryo Anai, YoshitakaShirasago, Kyoko Saito, Yuko Murakami,Hidesuke Fukazawa, Tetsuro Suzuki, TakajiWakita, Jo Chiba, Kentaro Hanada
  • Organizer: The 19th International Symposium on Hepatitis C Virus andRelated Viruses
  • Place of Presentation: Italy
• [Presentation] ヒトTRAX蛋白質の発現量の制御
  • Author(s): 白砂圭崇
  • Organizer: 日本薬学会第１３２年会
  • Place of Presentation: 北海道大学（北海道）
• [Book] Stem Cells and Human Diseases Translin/TRAX deficiency affects mesenchymal differentiation programs and induces bone marrow failure. (2012)
  • Author(s): Ishida R, Aoki K, Nakahara K, Fukuda Y, Ohori M, Saito Y, Kano K, Matsuda J, Asano S, Maziarz RT, Kasai M.
  • Total Pages: 9
  • Publisher: Springer-Verlag