Defensive mechanism of interferon-regulatory factors (IRFs) via trypsinogens against virus infection.

• Project/Area Number: 24590555
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Virology
• Research Institution: Nagasaki University
• Principal Investigator: HAYASHI Hideki 長崎大学, 医歯薬学総合研究科(医学系), 准教授 (10218589)
• Co-Investigator(Kenkyū-buntansha): KUBO Yoshinao 長崎大学, 医歯薬学総合研究科(医学系), 准教授 (30273527)
• Co-Investigator(Renkei-kenkyūsha): MATSUYAMA Toshifumi 長崎大学, 医歯薬学総合研究科(医学系), 教授 (30165922)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: インフルエンザウイルス / トリプシノーゲン / エンテロキナーゼ / インターフェロン調節因子(IRFs) / インターフェロン誘導遺伝子(ISGs) / インターフェロン誘導遺伝子 / インターフェロン調節因子 / インターフェロン調節因子IRFs / トリプシノーゲン遺伝子 / A型インフルエンザ・ウイルス / インターフェロン誘導遺伝子ISGs / A型インフルエンザウイルス

Outline of Final Research Achievements

We have shown the expressions of enterokinase in many human cells other than duodenal cells where it activates trypsinogens secreted from the pancreas. In addition, some types of trypsinogens are reported to exist in many cells as well as pancreatic cells. Our data indicated that the enterokinase significantly enhanced the influenza A virus infection by activating the trypsinogens. The enterokinase-mediated activation of trypsinogens could be a target for the development of new anti-viral reagents against influenza A virus.

Research Products

• [Journal Article] Androgen-independent proliferation of LNCaP prostate cancer cells infected by xenotropic murine leukemia virus-related virus. (2014)
  • Author(s): Kakoki K, Kamiyama H, Izumida M, Yashima Y, Hayashi H, Yamamoto N, Matsuyama T, Igawa T, Sakai H, Kubo Y.
  • Journal Title: Biochem Biophys Res Commun. Volume: 447 Issue: 1 Pages: 216-222
  • DOI: 10.1016/j.bbrc.2014.03.154
  • NAID: 120006986603
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Susceptibility of muridae cell lines to ecotropic murine leukemia virus and the cationic amino acid transporter 1 viral receptor sequences: implications for evolution of the viral receptor. (2014)
  • Author(s): Kakoki K, Shinohara A, Izumida M, Koizumi Y, Honda E, Kato G, Igawa T, Sakai H, Hayashi H, Matsuyama T, Morita T, Koshimoto C, Kubo Y.
  • Journal Title: Virus Genes. Volume: 48 Issue: 3 Pages: 448-456
  • DOI: 10.1007/s11262-014-1036-1
  • NAID: 120006986554
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] SAM domain-containing N-terminal region of SAMHD1 plays a crucial role in its stabilization and restriction of HIV-1 infection (2014)
  • Author(s): Shigematsu S, Hayashi H, Yasui K, Matsuyama T.
  • Journal Title: Acta Med Nagasaki Volume: 58 Pages: 103-111
  • NAID: 130004879524
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] CXCR4-tropic, but not CCR5-tropic, human immunodeficiency virus infection is inhibited by the lipid raft-associated factors, acyclic retinoid analogs, and cholera toxin B subunit (2013)
  • Author(s): H. Kamiyama, K. Kakoki, S. Shigematsu, M. Izumida, Y. Yashima, Y. Tanaka, H. Hayashi, T. Matsuyama, H. Sato, N. Yamamoto, T. Sano, Y. Shidoji, Y. Kubo
  • Journal Title: AIDS Res.Hum.Retrovir. Volume: 29 Issue: 2 Pages: 279-88
  • DOI: 10.1089/aid.2012.0174
  • NAID: 120006985740
  • Peer Reviewed
• [Journal Article] A short variant BTBD2 as a novel negative regulator of IRF-associated signalling. (2013)
  • Author(s): Chua KJ, Kubo Y, Ma Y, Yasui K, Matsuyama T, and Hayashi H.
  • Journal Title: Int J Integrative Biol Volume: 14 Pages: 3138-3138
  • Peer Reviewed
• [Journal Article] Serum starvation activates NF-kB through G protein B2 subunit-mediated signal (2012)
  • Author(s): T. Kohno, Y. Kubo, K. Yasui, M. Haraguchi, S. Shigematsu, K.J. Chua, T. Matsuyama, H. Hayashi.
  • Journal Title: DNA Cell Biol Volume: 31 Issue: 11 Pages: 1636-44
  • DOI: 10.1089/dna.2012.1666
  • Peer Reviewed
• [Journal Article] Retrovirus entry by endocytosis and cathepsinproteases. (2012)
  • Author(s): Y. Kubo, H. Hayshi, T. Matsuyama, H. Sato, N. Yamamoto.
  • Journal Title: Adv.Virol. Volume: 2012 Pages: 640894-640894
  • DOI: 10.1155/2012/640894
  • NAID: 120006985742
  • Peer Reviewed
• [Presentation] インターフェロンによるレトロウイルス感染抑制に関与する新規細胞性因子の同定 (2014)
  • Author(s): 久保嘉直、泉田真生、安井潔、林日出喜、松山俊文
  • Organizer: 第62回日本ウイルス学会学術総会
  • Place of Presentation: パシフィコ横浜(横浜市)
  • Year and Date: 2014-11-10 – 2014-11-12
• [Presentation] インターフェロンG誘導遺伝子GILTによるHIV粒子産物抑制機構の解明 (2013)
  • Author(s): 久保嘉直、神山陽香、泉田真生、田中勇悦、安井潔、佐藤祐徳、山本直樹、松山俊文、林日出喜
  • Organizer: 第61回日本ウイルス学会学術総会
  • Place of Presentation: 神戸国際会議場 (神戸市中央区)
• [Presentation] Identification of poly(I:C)-induced pancreatitis- related genes in IRF2-deficient mice (2012)
  • Author(s): Hayashi H
  • Organizer: 3rd International conference on“Current advances in Microbiology and Immunology”
  • Place of Presentation: ULAANBAATAR, MONGOLIA
  • Invited
• [Presentation] ATL細胞株の細胞死をTRAIL-依存性に促進させる生物活性物質のスクリーニング (2012)
  • Author(s): 林日出喜、長谷川寛雄、河野友子、中尾一彦、 松山俊文
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] 血清枯渇はG Protein β2を介したNF-κB経路を活性化する (2012)
  • Author(s): 安井 潔, 河野友子、久保嘉直、原口恵、重松小百合、蔡君柔、松山俊文、林日出喜
  • Organizer: 第35回日本分子生物学会
  • Place of Presentation: マリンメッセ福岡