Molecular basis for cell entry of canine distemper virus

• Project/Area Number: 15H02384
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Structural biochemistry
• Research Institution: Hokkaido University
• Principal Investigator: MAENAKA Katsumi 北海道大学, 薬学研究院, 教授 (10322752)
• Co-Investigator(Kenkyū-buntansha): 福原 秀雄 北海道大学, 薬学研究院, 特任助教 (80707191)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥38,220,000 (Direct Cost: ¥29,400,000、Indirect Cost: ¥8,820,000); Fiscal Year 2017: ¥11,830,000 (Direct Cost: ¥9,100,000、Indirect Cost: ¥2,730,000); Fiscal Year 2016: ¥11,570,000 (Direct Cost: ¥8,900,000、Indirect Cost: ¥2,670,000); Fiscal Year 2015: ¥14,820,000 (Direct Cost: ¥11,400,000、Indirect Cost: ¥3,420,000)
• Keywords: 構造解析 / ウイルス / 細胞侵入 / 細胞表面受容体 / 相互作用解析 / X線結晶構造解析 / 膜融合 / ワクチン / 生物物理 / 電子顕微鏡解析 / 中和抗体 / 抗体 / ジステンパーウイルス / 蛋白質 / 免疫学 / 構造生物学

Outline of Final Research Achievements

The structural features of the membrane fusion protein (CDV-F) of canine distemper virus (CDV) were observed by cryo-electron microscopy. The sample preparation and grid manufacturing conditions were successfully optimized for high-resolution analysis. On the other hand, for the receptor-binding protein (CDV-H) of the same virus, several anti-CDV-H monoclonal antibodies were setablished by rat intestinal lymph node method. The subtypes and CDV-H binding properties of the obtained antibodies were examined. The membrane fusion assay showed that each antibody has different binding affinity and specificity. These results give insight on the molecular basis of viral entry and vaccine effectiveness of CDV and related viruses.

Research Products

• [Int'l Joint Research] ベルン大学(スイス)
• [Int'l Joint Research] オックスフォード大学(英国)
• [Journal Article] The immunosuppressive effect of domain-deleted dimer of HLA-G2 isoform in collagen-induced arthritis mice. (2016)
  • Author(s): Takahashi A, Kuroki K, Okabe Y, Kasai Y, Matsumoto N, Yamada C, Takai T, Ose T, Kon S, Matsuda T, Maenaka K.
  • Journal Title: Hum Immunol. Volume: S0198-8859 Issue: 9 Pages: 00011-2
  • DOI: 10.1016/j.humimm.2016.01.010
  • NAID: 120006337746
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Osteopontin-integrin interaction as a novel molecular target for antibody-mediated immunotherapy in adult T-cell leukemia. (2015)
  • Author(s): 1.Maeda N, Ohashi T, Chagan-Yasutan, H, Hattori T, Takahashi Y, Harigae, H, Hasegawa H, Yamada Y, Fujii M, Maenaka K, and Uede T.
  • Journal Title: Retrovirology Volume: 12 Issue: 1 Pages: 99-99
  • DOI: 10.1186/s12977-015-0225-x
  • Peer Reviewed / Open Access
• [Journal Article] The cell competition-based high-throughput screening identifies small compounds that promote the elimination of RasV12-transformed cells from epithelia. (2015)
  • Author(s): Yamauchi, H., Matsumaru, T., Morita, T., Ishikawa, S., Maenaka, K., Takigawa, I., Semba, K., Kon, S. and Fujita, Y.
  • Journal Title: Scientific Reports Volume: 5 Issue: 1 Pages: 15336-15336
  • DOI: 10.1038/srep15336
  • NAID: 120005674073
  • Peer Reviewed / Open Access
• [Presentation] モリビリウイルス属の細胞侵入機構の構造基盤と阻害剤開発 (2016)
  • Author(s): 前仲勝実
  • Organizer: 日本薬学会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-03-28
  • Invited
• [Presentation] モリビリウイルス属の細胞侵入の構造基盤と抗ウイルス薬開発 (2016)
  • Author(s): 前仲勝実
  • Organizer: 平成27年度 京都大学ウイルス研究所・再生医科学研究所 合同学術講演会
  • Place of Presentation: 京都大学（京都府京都市）
  • Year and Date: 2016-01-21
  • Invited
• [Presentation] Molecular recognition of glycopeptides by human immune receptor, PILR. (2015)
  • Author(s): Maenaka Katsumi
  • Organizer: 第38回日本分子生物学会年会、第88回日本生化学会大会 合同大会
  • Place of Presentation: 神戸国際会議場（兵庫県神戸市）
  • Year and Date: 2015-12-01
  • Invited
• [Remarks] 北海道大学大学院薬学研究院生体分子機能学研究室
  • URL: http://convallaria.pharm.hokudai.ac.jp/bunshi/
• [Remarks] 北海道大学大学院薬学研究院創薬科学研究教育センター
  • URL: http://japanese-apricot.pharm.hokudai.ac.jp/