Research of neutralizing antibody recognizing glycopeptides onto hepatitis C virus and basic studies for new diagnoses

• Project/Area Number: 25293134
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: National Institute of Advanced Industrial Science and Technology
• Principal Investigator: Shimizu Hiroki 国立研究開発法人産業技術総合研究所, 生物プロセス研究部門, 主任研究員 (30344716)
• Co-Investigator(Kenkyū-buntansha): 奥田 徹哉 国立研究開発法人産業技術総合研究所, 生物プロセス研究部門, 主任研究員 (20443179) ; 鈴木 哲朗 浜松医科大学, 医学部, 教授 (00250184) ; 松岡 浩司 埼玉大学, 理工学研究科, 教授 (40272281) ; 松尾 一郎 群馬大学, 大学院理工学府, 教授 (40342852)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000); Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2015: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2014: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2013: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
• Keywords: Ｃ型肝炎 / 糖ペプチド / 糖鎖 / 抗体 / 糖 / C型肝炎

Outline of Final Research Achievements

The aim of this project was research of neutralizing antibody recognizing glycopeptides onto hepatitis C virus (HCV) and basic studies for new diagnoses.
We tried to produce a neutralizing antibody which recognize glycopeptide in E2 glycoprotein onto HCV. The first stage, to synthesize glycopeptide antigen having developed (by Okuda et al) immunization tag, faced many difficulties, but finally, we achieved to synthesize the designed glycopepitde antigen with aid of new microwave techniques which Shimizu et al developed. Then, immunization was performed and currently produced antibodies are evaluated.

Research Products

• [Journal Article] Localized surface plasmon resonance-mediated fluorescence signals in plasmonic nanoparticle-quantum dot hybrids for ultrasensitive Zika virus RNA detection via hairpin hybridization assays. (2017)
  • Author(s): Adegoke O, Morita M, Kato T, Ito M, Suzuki T, Park EY.
  • Journal Title: Biosens Bioelectron. Volume: 94 Pages: 513-522
  • DOI: 10.1016/j.bios.2017.03.046
  • NAID: 120006542499
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Nonstructural 5A Protein of Hepatitis C Virus Interferes with Toll-Like Receptor Signaling and Suppresses the Interferon Response in Mouse Liver. (2017)
  • Author(s): Tsutsumi T, Okushin K, Enooku K, Fujinaga H, Moriya K, Yotsuyanagi H, Aizaki H, Suzuki T, Matsuura Y, Koike K.
  • Journal Title: PLOS One Volume: 12 Issue: 1 Pages: 2017-2017
  • DOI: 10.1371/journal.pone.0170461
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Synthetic Assembly of Mannose Moieties using Polymer Chemistry and the Biological Evaluation of its Interaction towards Concanavalin A (2017)
  • Author(s): D. Diwan, K. Shinkai, T. Tetsuka, B. Cao, H. Arai, T. Koyama, K. Hatano, and K. Matsuoka
  • Journal Title: Molecules Volume: 22 Issue: 1 Pages: 157-157
  • DOI: 10.3390/molecules22010157
  • Peer Reviewed / Open Access
• [Journal Article] Biological Evaluation of Multivalent-Type N-Acetyl-D-Glucosamine (GlcNAc) Conjugates for Wheat Germ Agglutinin (WGA) by the Surface Plasmon Resonance (SPR) Method (2017)
  • Author(s): A. Kumari, T. Koyama, K. Hatano, and K. Matsuoka
  • Journal Title: SOJ Biochem Volume: 2 Issue: 3 Pages: 7-7
  • DOI: 10.15226/2376-4589/2/3/00118
  • Peer Reviewed / Open Access
• [Journal Article] LUC7L3/CROP inhibits replication of hepatitis B virus via suppressing enhancer II/basal core promoter activity. (2016)
  • Author(s): Li Y, Ito M, Sun S, Chida T, Nakashima K, Suzuki T.
  • Journal Title: Sci Rep Volume: 6 Issue: 1 Pages: 36741-36741
  • DOI: 10.1038/srep36741
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Synthetic Aassembly of Novel Avidin-biotin-GlcNAc (ABG) Complex as an Attractive Bio-probe and its Interaction with Wheat Germ Agglutinin (WGA) (2016)
  • Author(s): A. Kumari, T. Koyama, K. Hatano, and K. Matsuoka
  • Journal Title: Bioorg. Chem. Volume: 68 Pages: 219-225
  • DOI: 10.1016/j.bioorg.2016.08.002
  • Peer Reviewed
• [Journal Article] Single-domain Intrabodies against HCV Core Inhibit Viral Propagation and Core-induced NF-κB Activation (2016)
  • Author(s): Suzuki R, Saito K, Matsuda M, Sato M, Kanegae Y, Shi G, Watashi K, Aizaki H, Chiba J, Saito I, Wakita T, Suzuki T
  • Journal Title: J Gen Virol Volume: 印刷中 Issue: 4 Pages: 887-892
  • DOI: 10.1099/jgv.0.000423
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Involvement of the 3' Untranslated Region in Encapsidation of the Hepatitis C Virus (2016)
  • Author(s): Shi G, Ando T, Suzuki R, Matsuda M, Nakashima K, Ito M, Omatsu T, Oba M, Ochiai H, Kato T, Mizutani T, Sawasaki T, Wakita T, Suzuki T.
  • Journal Title: PLoS Pathog Volume: 12(2) Issue: 2 Pages: e1005441-e1005441
  • DOI: 10.1371/journal.ppat.1005441
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Monoclonal antibodies against extracellular domains of claudin-1 block hepatitis C virus infection in a mouse model (2015)
  • Author(s): Masayoshi Fukasawa, Shotaro Nagase, Yoshitaka Shirasago, Manami Iida, Mayo Yamashita, Kohki Endo, Kiyohito Yagi, Tetsuro Suzuki, Takaji Wakita, Kentaro Hanada, Hiroki Kuniyasu, Masuo Kondoh
  • Journal Title: J Virol Volume: 89 Issue: 9 Pages: 4866-4879
  • DOI: 10.1128/jvi.03676-14
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Targeting cellular squalene synthase, an enzyme essential for cholesterol biosynthesis is a potential antiviral strategy against hepatitis C virus (2015)
  • Author(s): Kyoko Saito, Yoshitaka Shirasago, Tetsuro Suzuki, Hideki Aizaki, Kentaro Hanada, Takaji Wakita, Masahiro Nishijima, Masayoshi Fukasawa
  • Journal Title: J. Virol. Volume: 89 Issue: 4 Pages: 2220-2232
  • DOI: 10.1128/jvi.03385-14
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Efficiency of 2.45 and 5.80 GHz microwave irradiation for a hydrolysis reaction by thermostable beta-Glucosidase HT1 (2014)
  • Author(s): Nagashima, Izuru; Sugiyama, Jun-ichi; Sakuta, Tomomi; Sasaki, Masahide; Shimizu, Hiroki
  • Journal Title: Biosci. Biotechnol. Biochem., Volume: 78 Issue: 5 Pages: 758-760
  • DOI: 10.1080/09168451.2014.891931
  • Peer Reviewed
• [Journal Article] Involvement of Hepatitis C Virus NS5A Hyperphosphorylation Mediated by Casein Kinase I-α in Infectious Virus Production. (2014)
  • Author(s): Masaki T, Matsunaga S, Takahashi H, Nakashima K, Kimura Y, Ito M, Matsuda M, Murayama A, Kato T, Hirano H, Endo Y, Lemon SM, Wakita T, Sawasaki T, Suzuki T
  • Journal Title: J Virol Volume: 88(13) Issue: 13 Pages: 7541-55
  • DOI: 10.1128/jvi.03170-13
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Alternative endocytosis pathway for productive entry of hepatitis C virus. (2014)
  • Author(s): Matsuda M, Suzuki R, Kataoka C, Watashi K, Aizaki H, Kato N, Matsuura Y, Suzuki T, Wakita T
  • Journal Title: J Gen Virol. Volume: 95(Pt 12) Issue: 12 Pages: 2658-67
  • DOI: 10.1099/vir.0.068528-0
  • Peer Reviewed / Open Access
• [Presentation] 糖鎖基質酵素反応におけるマイクロ波効果の研究 (2016)
  • Author(s): 長島生、作田智美、杉山順一、佐々木正秀、清水弘樹
  • Organizer: 日本農芸化学会2016年大会
  • Place of Presentation: 札幌コンベンションセンター（北海道）
  • Year and Date: 2016-03-29
• [Presentation] マイクロ波を使用したペプチド固相合成法の必要条件の検討 (2015)
  • Author(s): 山田隆哉、長島生、佐々木正秀、清水弘樹
  • Organizer: 平成27年度日本農芸化学会北海道支部第２回講演会
  • Place of Presentation: 北海道大学学術交流会館（北海道）
  • Year and Date: 2015-11-14
• [Presentation] 化学反応におけるマイクロ波特性とマイクロ波効果の活用 (2015)
  • Author(s): 清水弘樹
  • Organizer: 化学工学会第47回秋季大会
  • Place of Presentation: 北海道大学工学部（北海道）
  • Year and Date: 2015-09-09
  • Invited
• [Presentation] 反応容器による酵素反応の反応性差異 (2015)
  • Author(s): 清水弘樹、長島生
  • Organizer: バイオ分子科学研究会
  • Place of Presentation: 慶応義塾大学日吉キャンパス（神奈川県）
  • Year and Date: 2015-08-22
• [Presentation] beta-グルコース加水分解酵素反応における低周波マイクロ波効果の研究 (2015)
  • Author(s): 長島生、杉山順一、清水弘樹
  • Organizer: 日本農芸化学会2015年大会
  • Place of Presentation: 岡山大学津島キャンパス（岡山県）
  • Year and Date: 2015-03-29
• [Presentation] 糖加水分解酵素反応におけるマイクロ波の効果と作用機構解明研究 (2014)
  • Author(s): 長島生、作田智美、杉山順一、清水弘樹
  • Organizer: 第33回日本糖質学会年会
  • Place of Presentation: 名古屋大学豊田講堂（愛知県）
  • Year and Date: 2014-08-12
• [Presentation] 耐熱グルコシダーゼHT1酵素反応におけるマイクロ波効果の研究 (2014)
  • Author(s): 長島生、作田智美、杉山順一、佐々木正秀、清水弘樹
  • Organizer: 日本農芸化学会2014年大会
  • Place of Presentation: 明治大学（神奈川）
• [Presentation] アスパラギン結合型糖鎖生合成に関与するドリコールリン酸結合７糖の合成研究 (2013)
  • Author(s): 宇津井隆志、宮沢進平、岩本将吾、松尾一郎
  • Organizer: 第32回日本糖質学会年会
  • Place of Presentation: 大阪国際交流 センター（大阪）
• [Presentation] 分岐型4糖オキサゾリン誘導体を用いたendo-Mの基質特異性解析 (2013)
  • Author(s): 石井希実、岩本将吾、熊田純一、松崎祐二、松尾一郎
  • Organizer: 第32回日本糖質学会年会
  • Place of Presentation: 大阪国際交流 センター（大阪）
• [Presentation] 酵素反応へのマイクロ波利用研究
  • Author(s): 清水弘樹、長島生、作田智美
  • Organizer: 第4回グライコバイオロジクス研究会
  • Place of Presentation: 札幌市民ホール（札幌）
• [Book] 糖鎖の新機能開発応用ハンドブック、第4編 第1章 4-4 マイクロ波合成 (2015)
  • Author(s): 長島生、清水弘樹
  • Publisher: （株）エヌ・ティー・エス
• [Book] 最新 マイクロ波エネルギーと応用技術、第5章 5-3 生体高分子合成 (糖鎖、ペプチド、糖ペプチド) (2014)
  • Author(s): 長島生、清水弘樹
  • Publisher: ㈱産業技術サービスセンター