Identification of key molecule for influenza virus entry

• Project/Area Number: 16H06227
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Experimental pathology
• Research Institution: Hokkaido University
• Principal Investigator: Fujioka Yoichiro 北海道大学, 医学研究院, 講師 (70597492)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥25,090,000 (Direct Cost: ¥19,300,000、Indirect Cost: ¥5,790,000); Fiscal Year 2019: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2018: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2017: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2016: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
• Keywords: ウイルス / エンドサイトーシス / シグナル伝達 / カルシウム / インフルエンザウイルス / イメージング

Outline of Final Research Achievements

We have discovered that the Ca2+ channel, a transmembrane protein that allows Ca2+ to move across the plasma membrane, is the key receptor molecule for influenza virus infections. Furthermore, treating human cells with a calcium channel blocker (CCB), which is commonly used as anti-hypertension drug, significantly suppressed virus infections.

Academic Significance and Societal Importance of the Research Achievements

我々は従前のウイルス中心のインフルエンザ研究等とは異なり、宿主細胞側シグナル伝達をターゲットとした研究から、カルシウムチャネルがインフルエンザウイルス感染に鍵となる受容体タンパク質であると同定した。インフルエンザウイルス宿主侵入機構の全貌を解明した研究成果は高い評価を受けている。さらに、我々が提案する手法はこれまでの治療標的とは全く異なるプロセスである宿主細胞への“侵入”を標的とするため、新規治療法の開発に直結する可能性を秘めている。

Research Products

• [Journal Article] Calcium Wave Promotes Cell Extrusion (2020)
  • Author(s): Takeuchi Y、Narumi R、Akiyama R、Vitiello E、Shirai T、Tanimura N、Kuromiya K、Ishikawa S、Kajita M、Tada M、Haraoka Y、Akieda Y、 Ishitani T、Fujioka Y、Ohba Y、Yamada S、Hosokawa Y、Toyama Y、Matsui T、Fujita Y
  • Journal Title: Current Biology Volume: 30 Issue: 4 Pages: 670-681.e6
  • DOI: 10.1016/j.cub.2019.11.089
  • NAID: 120006960639
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A Peptide Derived from Phosphoinositide 3-kinase Inhibits Endocytosis and Influenza Virus Infection (2019)
  • Author(s): Fujioka Y, Satoh AO, Horiuchi K, Fujioka M, Tsutsumi K, Sasaki J, Nepal P, Kashiwagi S, Paudel S, Nishide S, Nanbo A, Sasaki T, Ohba Y
  • Journal Title: Cell Structure and Function Volume: 44 Issue: 1 Pages: 61-74
  • DOI: 10.1247/csf.19001
  • NAID: 130007636814
  • ISSN: 0386-7196, 1347-3700
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Folding Latency of Fluorescent Proteins Affects the Mitochondrial Localization of Fusion Proteins (2019)
  • Author(s): Sayaka Kashiwagi, Yoichiro Fujioka, Aya O. Satoh, Aiko Yoshida, Mari Fujioka, Prabha Nepal, Atsushi Tsuzuki, Ozora Aoki, Sarad Paudel, Hitoshi Sasajima, Yusuke Ohba
  • Journal Title: Cell Structure and Function Volume: 44 Issue: 2 Pages: 183-194
  • DOI: 10.1247/csf.19028
  • NAID: 130007775556
  • ISSN: 0386-7196, 1347-3700
  • Peer Reviewed / Open Access
• [Journal Article] Localization of BCR-ABL to Stress Granules Contributes to Its Oncogenic Function (2019)
  • Author(s): Sayaka Kashiwagi, Yoichiro Fujioka, Takeshi Kondo, Aya O. Satoh, Aiko Yoshida, Mari Fujioka, Hitoshi Sasajima, Maho Amano, Takanori Teshima, Yusuke Ohba
  • Journal Title: Cell Structure and Function Volume: 44 Issue: 2 Pages: 195-204
  • DOI: 10.1247/csf.19033
  • NAID: 130007775561
  • ISSN: 0386-7196, 1347-3700
  • Peer Reviewed / Open Access
• [Journal Article] Antibody-free digital influenza virus counting based on neuraminidase activity (2019)
  • Author(s): Tabata Kazuhito V.、Minagawa Yoshihiro、Kawaguchi Yuko、Ono Mana、Moriizumi Yoshiki、Yamayoshi Seiya、Fujioka Yoichiro、Ohba Yusuke、Kawaoka Yoshihiro、Noji Hiroyuki
  • Journal Title: Scientific Reports Volume: 9 Issue: 1 Pages: 1067-1067
  • DOI: 10.1038/s41598-018-37994-6
  • Peer Reviewed / Open Access
• [Journal Article] A Sialylated Voltage-Dependent Ca2+ Channel Binds Hemagglutinin and Mediates Influenza A Virus Entry into Mammalian Cells (2018)
  • Author(s): Fujioka Y, Nishide S, Ose T, Suzuki T, Kato I, Fukuhara H, Fujioka M, Horiuchi K, Satoh AO, Nepal P, Kashiwagi S, Wang J, Horiguchi M, Sato Y, Paudel S, Nanbo A, Miyazaki T, Hasegawa H, Maenaka K, Ohba Y
  • Journal Title: Cell Host Microbe Volume: 23 Issue: 6 Pages: 809-818
  • DOI: 10.1016/j.chom.2018.04.015
  • NAID: 120006643588
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Dermoscopic evaluation for skin grafts after surgery; neo-vascularization correlates with survival of skin grafts: A prospective study (2018)
  • Author(s): Kitamura Shinya、Yanagi Teruki、Inamura-Takashima Yuka、Imafuku Keisuke、Hata Hiroo、Fujioka Yoichiro、Ohba Yusuke、Shimizu Hiroshi
  • Journal Title: J Dermatol Sci Volume: 印刷中 Issue: 2 Pages: 213-216
  • DOI: 10.1016/j.jdermsci.2018.01.014
  • Peer Reviewed
• [Journal Article] Ebola virus requires a host scramblase for externalization of phosphatidylserine on the surface of viral particles (2018)
  • Author(s): Nanbo Asuka、Maruyama Junki、Imai Masaki、Ujie Michiko、Fujioka Yoichiro、Nishide Shinya、Takada Ayato、Ohba Yusuke、Kawaoka Yoshihiro
  • Journal Title: PLoS Pathog Volume: 14 Issue: 1 Pages: e1006848-e1006848
  • DOI: 10.1371/journal.ppat.1006848
  • NAID: 120006416019
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A leukemogenic kinase, FIP1L1-PDGFRA, and a SUMO E3 ligase, PIAS1, form a positive crosstalk via their enzymatic activities. (2017)
  • Author(s): M. Ibata, J. Iwasaki, Y. Fujioka, K. Nakagawa, S. Darmanin, M. Onozawa, D. Hashimoto, Y. Ohba, S. Hatakeyama, T. Teshima and T. Kondo.
  • Journal Title: Cancer Sci. Volume: 108 Issue: 2 Pages: 200-207
  • DOI: 10.1111/cas.13129
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Rab5-regulated endocytosis plays a crucial role in apical extrusion of transformed cells. (2017)
  • Author(s): S. Saitoh, T. Maruyama, Y. Yako, M. Kajita, Y. Fujioka, Y. Ohba, N. Kasai, N. Sugama, S. Kon, S. Ishikawa, T. Hayashi, T. Yamazaki, M. Tada and Y. Fujita.
  • Journal Title: Proc. Natl. Acad. Sci. U.S.A. Volume: 114 Issue: 12
  • DOI: 10.1073/pnas.1602349114
  • NAID: 120006346108
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Improved FRET Biosensor for the Measurement of BCR-ABL Activity in Chronic Myeloid Leukemia Cells (2017)
  • Author(s): M. Horiguchi, M. Fujioka, T. Kondo, Y. Fujioka, X. Li, K. Horiuchi, A.O. Satoh, P. Nepal, S. Nishide, A. Nanbo, T. Teshima and Y. Ohba.
  • Journal Title: Cell Structure and Function Volume: 42 Issue: 1 Pages: 15-26
  • DOI: 10.1247/csf.16019
  • NAID: 130005308488
  • ISSN: 0386-7196, 1347-3700
  • Peer Reviewed / Open Access
• [Journal Article] Cell competition with normal epithelial cells promotes apical extrusion of transformed cells through metabolic changes (2017)
  • Author(s): Kon S, Ishibashi K, Katoh H, Kitamoto S, Shirai T, Tanaka S, Kajita M, Yako Y, Nishikawa A, Kameda I, Sasaki Y, Enoki R, Honma S, Imamura H, Oshima M, Soga T, Miyazaki J, Duchen M R, Nam J-M, Onodera Y, Yoshioka S, Kikuta J, Ishii M, Imajo M, Nishida E, Fujioka Y, Ohba Y, Sato T, and Fujita Y
  • Journal Title: Nat. Cell Biol. Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Fluorescence bioimaging of intracellular signaling and its clinical application (2016)
  • Author(s): Ohba Y, and Fujioka Y
  • Journal Title: J. Oral Biosci. Volume: 58 Issue: 4 Pages: 113-119
  • DOI: 10.1016/j.job.2016.07.002
  • Peer Reviewed
• [Presentation] インフルエンザウイルス粒子の細胞取り込み機構の解析 (2019)
  • Author(s): 藤岡容一朗、佐藤絢、吉田藍子、笹島仁、サラドパウデル、皆川慶嘉、 田端和仁、野地博行、大場雄介
  • Organizer: 第42回日本分子生物学会年会
• [Presentation] A PI3K-derived peptide inhibits clathrin-independent endocytosis and influenza virus infection (2018)
  • Author(s): Yoichiro Fujioka, Aya O. Satoh, Kosui Horiuchi, Mari Fujioka, Sarad Paudel, Asuka Nanbo, Yusuke Ohba
  • Organizer: Joint Annual Meeting of JSDB 51st and JSCB 70th
  • Int'l Joint Research
• [Presentation] Identification of host cell proteins critical for influenza virus entry (2017)
  • Author(s): 藤岡容一朗、西出真也、藤岡真理、堀内浩水、佐藤絢、ネパール プラバ、柏木彩花、王セイ、堀口美香、パウデル サラド、南保明日香、大場雄介
  • Organizer: 第69回日本細胞生物学会大会
• [Presentation] A PI3K-derived peptide inhibits endocytosis and influenza virus infection (2017)
  • Author(s): 藤岡容一朗、佐藤絢、堀内浩水、藤岡真理、パウデル サラド、西出真也、南保明日香、大場雄介
  • Organizer: CONBIO2017
• [Presentation] Influenza viruses are internalized into host cells via calcium signaling-mediated endocytosis (2017)
  • Author(s): Fujioka Y, Nishide S, Ose T, Kato I, Fukuhara H, Fujioka M, Horiuchi K, Satoh A, Nepal P, Kashiwagi S, Wang J, Horiguchi M, Paudel S, Nanbo A, Miyazaki T, Maenaka K, Ohba Y
  • Organizer: 3rd International symposium on cell competition
  • Int'l Joint Research
• [Presentation] インフルエンザウイルス宿主細胞侵入を制御する宿主側因子の同定 (2016)
  • Author(s): 藤岡容一朗, 西出真也, 佐藤絢, 堀内浩水, ネパールプラバ, 堀口美香, 王セイ, 南保明日香, 大場雄介
  • Organizer: 第６８回日本細生物学会大会
  • Place of Presentation: 京都テルサ（京都府京都市）
  • Year and Date: 2016-06-15
• [Book] 実験医学 2017年12月号 (2017)
  • Author(s): 藤岡容一朗，田端和仁，大場雄介，野地博行他
  • Total Pages: 137
  • Publisher: 羊土社
  • ISBN: 9784758125024
• [Remarks] 北海道大学大学院医学研究院細胞生理学教室ホームページ
  • URL: http://cp.med.hokudai.ac.jp
• [Remarks] 北海道大学大学院医学研究院細胞生理学教室HP
  • URL: http://cp.med.hokudai.ac.jp
• [Remarks] 細胞生理学教室ホームページ
  • URL: http://cp.med.hokudai.ac.jp