Analysis of supressive role of complement factors in prion propagation

• Project/Area Number: 26450397
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Veterinary medical science
• Research Institution: Hokkaido University
• Principal Investigator: Hasebe Rie 北海道大学, 獣医学研究院, 講師 (70431335)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: プリオン病 / 補体因子 / 神経病態

Outline of Final Research Achievements

Roles of complement factors in neuropathogenesis of prion diseases are unknown. The results of the current study suggest that the amount of abnormal form of prion protein (PrPSc) was reduced in Chandler-infected primary cultured neurons, but was increased in 22L-infected neurons after temporary decrease. To assess the effects of complement reaction in in vivo prion infection, I injected lentivirus vectors harboring shRNA against complement factors C1qA and C3 into prion-infected mouse brains. In Chandler-infected mice, PrPSc was increased after C1q- and C3-shRNA injection. In contrast, PrPSc was decreased in 22L-infected mouse brains after C3-shRNA injection, but not C1qA-shRNA injection. These results suggest that the type and the effect of complement factors on the neuropathogenesis were different among the prion strains

Research Products

• [Journal Article] Complement factors alter the amount of PrP(Sc) in primary-cultured mouse cortical neurons associated with increased membrane permeability (2016)
  • Author(s): Hasebe R, Tanaka M, Suzuki A, Yamasaki T, Horiuchi M
  • Journal Title: Virology Volume: 496 Pages: 9-20
  • DOI: 10.1016/j.virol.2016.05.014
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Comparison of abnormal isoform of prion protein in prion-infected cell lines and primary-cultured neurons by PrPSc-specific immunostaining (2016)
  • Author(s): Tanaka M, Fujiwara A, Suzuki A, Yamasaki T, Hasebe R, Masujin K, Horiuchi M
  • Journal Title: J Gen Virol Volume: 97 Issue: 8 Pages: 030-2042
  • DOI: 10.1099/jgv.0.000514
  • NAID: 120006331855
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Establishment of a simple cell-based ELISA for the direct detection of abnormal isoform of prion protein from prion-infected cells without cell lysis and proteinase K treatment (2016)
  • Author(s): Shan Z, Yamasaki T, Suzuki A, Hasebe R, Horiuchi M
  • Journal Title: Prion Volume: 10 Issue: 4 Pages: 305-318
  • DOI: 10.1080/19336896.2016.1189053
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Temporary upregulation of anti-inflammatory cytokine IL-13 expression in the brains of CD14 deficient mice in the early stage of prion infection. (2014)
  • Author(s): Hasebe R, Suzuki A, Yamasaki T, Horiuchi M
  • Journal Title: Biochem Biophys Res Commun Volume: 454 Issue: 1 Pages: 125-130
  • DOI: 10.1016/j.bbrc.2014.10.043
  • NAID: 120005540293
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Comparison of the anti-prion mechanism of four different anti-prion compounds, anti-PrP monoclonal antibody 44B1, pentosan polysulfate, chlorpromazine, and U18666A, in prion-infected mouse neuroblastoma cells. (2014)
  • Author(s): Yamasaki T, Suzuki A, Hasebe R, Horiuchi M
  • Journal Title: PLoS One Volume: 9 Issue: 9 Pages: e106516-e106516
  • DOI: 10.1371/journal.pone.0106516
  • NAID: 120005476205
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Autophagy inhibits viral genome replication and gene expression stages in West Nile virus infection. (2014)
  • Author(s): Kobayashi S, Orba Y, Yamaguchi H, Takahashi K, Sasaki M, Hasebe R, Kimura T, Sawa H.
  • Journal Title: Virus Res Volume: 191 Pages: 83-91
  • DOI: 10.1016/j.virusres.2014.07.016
  • NAID: 120005517727
  • Peer Reviewed
• [Journal Article] Tick-borne flaviviruses alter membrane structure and replicate in dendrites of primary mouse neuronal cultures. (2014)
  • Author(s): Minato Hirano, Kentaro Yoshii, Mizuki Sakai, Rie Hasebe, Osamu Ichii and Hiroaki Kariwa
  • Journal Title: JOURNAL OF GENERAL VIROLOGY Volume: 95 Issue: 4 Pages: 849-861
  • DOI: 10.1099/vir.0.061432-0
  • Peer Reviewed
• [Presentation] Neuron and glial cell type-specific detection of PrPSc in prion-infected mouse brain by flow cytometry. (2016)
  • Author(s): Yamasaki T, Suzuki A, Hasebe R, Horiuchi M
  • Organizer: 第64回日本ウイルス学会学術集会
  • Place of Presentation: 北海道、札幌
  • Year and Date: 2016-09-23
• [Presentation] Analysis of activation state of microglia and astrocytes in prion-infected mice by RNA-sequencing (2016)
  • Author(s): Kuroda M, Yamasaki T, Hasebe R, Suzuki A, Horiuchi M
  • Organizer: 第64回日本ウイルス学会学術集会
  • Place of Presentation: 北海道、札幌
  • Year and Date: 2016-09-23
• [Presentation] Utility of cervid recombinant PrP for the detection of L-BSE and CWD prions by RT-QuIC. (2016)
  • Author(s): Suzuki A, Yamasaki T, Hasebe R, Horiuchi M
  • Organizer: 第64回日本ウイルス学会学術集会
  • Place of Presentation: 北海道、札幌
  • Year and Date: 2016-09-23
• [Presentation] 北大農場で発生したリステリア症罹患羊の飼育環境からのリステリア属菌の分離とゲノム解析 (2016)
  • Author(s): 長谷部 理絵, 青島 圭佑, 棟居 佳子, 三谷 朋弘, 平井 佑治, 山﨑 剛士, 木村 享史, 堀内 基広
  • Organizer: 第159回日本獣医学会学術集会
  • Place of Presentation: 神奈川県、藤沢
  • Year and Date: 2016-09-06
• [Presentation] リステリアモノサイトゲネスの腸管上皮細胞モデルとの相互作用解析と分子遺伝学的解析 (2016)
  • Author(s): 平井 佑治, 神吉 政史, 長谷川 めぐみ, 池田 徹也, 長谷部 理絵, 堀内 基広
  • Organizer: 第159回日本獣医学会学術集会
  • Place of Presentation: 神奈川県、藤沢
  • Year and Date: 2016-09-06
• [Presentation] 異常型プリオンタンパク質 (PrPSc) 特異的染色法によるプリオン持続感染株化細胞とプリオン感染初代培養神経細胞におけるPrPScの解析 (2016)
  • Author(s): 田中 美咲, 舛甚 賢太郎, 山﨑 剛士, 長谷部 理絵, 鈴木 章夫, 堀内 基広
  • Organizer: 第159回日本獣医学会学術集会
  • Place of Presentation: 神奈川県、藤沢
  • Year and Date: 2016-09-06
• [Presentation] 次世代シーケンサーを用いた、プリオン感染マウス脳由来ミクログリアおよびアストロサイトの活性化状態の解析 (2016)
  • Author(s): 黒田 弥乃梨, 山﨑 剛士, 鈴木 章夫, 長谷部 理絵, 堀内 基広
  • Organizer: 第159回日本獣医学会学術集会
  • Place of Presentation: 神奈川県、藤沢
  • Year and Date: 2016-09-06
• [Presentation] Neuron and glial cell type-specific detection of PrPSc in prion-infected mouse brain by flow cytometry. (2016)
  • Author(s): Yamasaki T, Suzuki A, Hasebe R, Horiuchi M
  • Organizer: Prion2016
  • Place of Presentation: Chiyoda-ku, Tokyo, Japan
  • Year and Date: 2016-05-10
  • Int'l Joint Research
• [Presentation] Transcriptome analysis of microglia and astrocytes in prion-infected mice (2016)
  • Author(s): Kuroda M, Yamasaki T, Suzuki A, Hasebe R , Horiuchi M
  • Organizer: Prion2016
  • Place of Presentation: Chiyoda-ku, Tokyo, Japan
  • Year and Date: 2016-05-10
  • Int'l Joint Research
• [Presentation] Comparison of abnormal isoform of prion protein in prion-infected cell lines and primary cultured neurons by PrPSc-specific immunostaining (2016)
  • Author(s): Tanaka M, Fujiwara A, Suzuki A, Yamasaki T, Hasebe R, Masujin K, Horiuchi M
  • Organizer: Prion2016
  • Place of Presentation: Chiyoda-ku, Tokyo, Japan
  • Year and Date: 2016-05-10
  • Int'l Joint Research
• [Presentation] Comparison of PrPSc-specific staining with two anti-PrP monoclonal antibodies 132 and 8D5 in immuno-cytochemistry (2015)
  • Author(s): Tanaka, M., Masujin, K., Yamasaki, T., Suzuki, A., Hasebe, R., and Horiuchi, M
  • Organizer: The 63rd Annual Meeting of The Japanese Sciety for Virology
  • Place of Presentation: Fukuoka, Fukuoka, Japan
  • Year and Date: 2015-11-22
• [Presentation] Comparison of PrPSc-specific staining with two anti-PrP monoclonal antibodies in immuno-cytochemistry (2015)
  • Author(s): Tanaka, M., Masujin, K., Yamasaki, T., Suzuki, A., Hasebe, R., and Horiuchi, M
  • Organizer: APPS2015
  • Place of Presentation: Kanazawa, Ishikawa, Japan
  • Year and Date: 2015-09-04
  • Int'l Joint Research
• [Presentation] Increased membrane permeability by complement factors affect PrPSc deposition in neurons (2015)
  • Author(s): Hasebe, R., Suzuki, A., Yamasaki, T., and Horiuchi, M.
  • Organizer: Prion2015
  • Place of Presentation: Fort Collins, Colorado, USA
  • Year and Date: 2015-05-26
  • Int'l Joint Research
• [Presentation] Analysis of activation state of astrocytes with the progression of prion diseases (2015)
  • Author(s): Kuroda, M., Yamasaki, T.,Suzuki, A., Hasebe, R., and Horiuchi, M
  • Organizer: Prion2015
  • Place of Presentation: Fort Collins, Colorado, USA
  • Year and Date: 2015-05-26
  • Int'l Joint Research
• [Presentation] Highthrouput detection of PrPSc from prion-infected cells without PK treatment: Cell-based ELISA for novel screening method for anti-prion compounds (2015)
  • Author(s): Shan, Z., Yamasaki, T., Suzuki, A., Hasebe, R., and Horiuchi, M
  • Organizer: Prion2015
  • Place of Presentation: Fort Collins, Colorado, USA
  • Year and Date: 2015-05-26
  • Int'l Joint Research
• [Presentation] Flow cytometric detection of PrPSc in neurons from prion-infected mouse brain (2015)
  • Author(s): Yamasaki, T., Suzuki, A., Hasebe, R., and Horiuchi, M
  • Organizer: Prion2015
  • Place of Presentation: Fort Collins, Colorado, USA
  • Year and Date: 2015-05-26
  • Int'l Joint Research
• [Presentation] プリオンの増殖に関わる細胞内小器官の同定ープリオン感染マウス脳組織の免疫組織学的解析からー (2014)
  • Author(s): 堀内 基広、斉藤 真央、長谷部 理絵、山崎 剛士
  • Organizer: 第62回日本ウイルス学会学術集会
  • Place of Presentation: パシフィコ横浜、神奈川県
  • Year and Date: 2014-11-10 – 2014-11-12
• [Presentation] フローサイトメトリーによるプリオン感染細胞の検出 (2014)
  • Author(s): 山崎 剛士、鈴木 章夫、長谷部 理絵、堀内 基広
  • Organizer: 第62回日本ウイルス学会学術集会
  • Place of Presentation: パシフィコ横浜、神奈川県
  • Year and Date: 2014-11-10 – 2014-11-12
• [Presentation] 補対反応はプリオン感染マウス大脳皮質由来初代培養神経細胞の細胞膜透過性を亢進し、異常型プリオンタンパク質の蓄積量を変化させる (2014)
  • Author(s): 長谷部 理絵、鈴木 章夫、山崎 剛士、堀内 基広
  • Organizer: 第62回日本ウイルス学会学術集会
  • Place of Presentation: パシフィコ横浜、神奈川県
  • Year and Date: 2014-11-10 – 2014-11-12
• [Presentation] プリオンの病態進行に伴うアストロサイト活性化状態の解析 (2014)
  • Author(s): 黒田 弥乃梨、山崎 剛士、鈴木 章夫、長谷部 理絵、堀内 基広
  • Organizer: 第62回日本ウイルス学会学術集会
  • Place of Presentation: パシフィコ横浜、神奈川県
  • Year and Date: 2014-11-10 – 2014-11-12
• [Presentation] プリオン感染マウス脳由来アストロサイトの活性化状態の解析 (2014)
  • Author(s): 黒田 弥乃梨、山崎 剛士、鈴木 章夫、長谷部 理絵、堀内 基広
  • Organizer: 第157回日本獣医学会学術集会
  • Place of Presentation: 北海道大学、北海道
  • Year and Date: 2014-09-09 – 2014-09-12
• [Presentation] 大脳皮質由来初代培養神経細胞におけるプリオン感染の解析 (2014)
  • Author(s): 藤原 愛、山崎 剛士、鈴木 章夫、長谷部 理絵、堀内 基広
  • Organizer: 第157回日本獣医学会学術集会
  • Place of Presentation: 北海道大学、北海道
  • Year and Date: 2014-09-09 – 2014-09-12
• [Presentation] Comparison of anti-prion mechanism of four different anti-prion compounds, anti-monoclonal antibody 44B1, pentosan polysulfate, chlorpromazine and U18666A in prion-infected mouse neuroblastoma cells (2014)
  • Author(s): Yamasaki T, Suzuki A, Hasebe R, Horiuchi M
  • Organizer: Asian Pacific Prion Symposium
  • Place of Presentation: Jeju International Convention Center, Kore
  • Year and Date: 2014-07-06 – 2014-07-07
• [Presentation] Analysis of prion infection in primary cortical neurons (2014)
  • Author(s): Fujiwara A, Sassa Y, Yamasaki T, Hasebe R, Horiuchi M
  • Organizer: Asian Pacific Prion Symposium
  • Place of Presentation: Jeju International Convention Center, Korea
  • Year and Date: 2014-07-06 – 2014-07-07
• [Presentation] High throughput detection of PrPSc from prion-infected cells without PK-treatment: cell based ELISA for novel screening for anti-prion compounds (2014)
  • Author(s): Shan Z, Yamasaki T, Suzuki A, Hasebe R, Horiuchi M
  • Organizer: Asian Pacific Prion Symposium
  • Place of Presentation: Jeju International Convention Center, Korea
  • Year and Date: 2014-07-06 – 2014-07-07
• [Presentation] Reaction kinetic analysis of anti-PrP monoclonal antibody mAb 132 by surface plasmon resonance (2014)
  • Author(s): Suzuki A, Yamasaki T, Hasebe R, Horiuchi M
  • Organizer: Asian Pacific Prion Symposium
  • Place of Presentation: Jeju International Convention Center, Korea
  • Year and Date: 2014-07-06 – 2014-07-07