Understanding the mechanism by which an interfeon-gamma-induced, mitochondria-localized novel protein inhibits virus infection

• Project/Area Number: 15K08499
• 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: KUBO Yoshinao 長崎大学, 医歯薬学総合研究科(医学系), 准教授 (30273527)
• Co-Investigator(Kenkyū-buntansha): 安井 潔 長崎大学, 医歯薬学総合研究科(医学系), 助教 (50372777)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: HIV / インターフェロン / IDO1 / FAT10 / IFI6 / interferon

Outline of Final Research Achievements

Hosts contain factors that inhibit virus infection, but many host anti-virus factors are waiting to be identified. In this research, we aimed to identify novel host anti-virus factors. This study would contribute to development of novel therapy against virus infection. Because many of such anti-virus factors are induced by interferon, we first identify interferon-induced factors by microarray. Then, impacts of the interferon-induced factors on human immunodeficiency virus (HIV) infection was comprehensively analyzed. As the result, we found that IFI6, FAT10, and IDO1 inhibit HIV infection. IDO1 catalizes one of the essential amino acids, tryptophan, and induces autophagy. IDO1 inhibits HIV infection through tryptophan depletion-induced autophagy.

Research Products

• [Journal Article] Enterokinase Enhances Influenza A Virus Infection by Activating Trypsinogen in Human Cell Lines. (2018)
  • Author(s): Hayashi H, Kubo Y, Izumida M, Takahashi E, Kido H, Sato K, Yamaya M, Nishimura H, Nakayama K, Matsuyama T.
  • Journal Title: Front Cell Infect Microbiol Volume: 8 Pages: 91-91
  • DOI: 10.3389/fcimb.2018.00091
  • NAID: 120006937672
  • Peer Reviewed / Open Access
• [Journal Article] Rab3a-Bound CD63 Is Degraded and Rab3a-Free CD63 Is Incorporated into HIV-1 Particles. (2017)
  • Author(s): Kubo Y, Masumoto H, Izumida M, Kakoki K, Hayashi H, Matsuyama T
  • Journal Title: Front Microbiol Volume: 29 Pages: 1653-1653
  • DOI: 10.3389/fmicb.2017.01653
  • NAID: 120006987411
  • Peer Reviewed / Open Access
• [Journal Article] Gamma-interferon-inducible, lysosome/endosome-localized thiolreductase, GILT, has anti-retroviral activity and its expression is counteracted by HIV-1 (2016)
  • Author(s): Y. Kubo, M. Izumida, Y. Yashima, H. Yoshii-Kamiyama, Y. Tanaka, K. Yasui, H. Hayashi, T. Matsuyama
  • Journal Title: Oncotarget Volume: 7 Issue: 44 Pages: 71255-71273
  • DOI: 10.18632/oncotarget.12104
  • NAID: 120006847273
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Fragments of target cells are internalized into retroviral envelope protein-expressing cells during cell-cell fusion by endocytosis. (2016)
  • Author(s): M. Izumida, H. Kamiyama, T. Suematsu, E. Honda, Y. Koizumi, K. Yasui, H. Hayashi, K. Ariyoshi, Y. Kubo
  • Journal Title: Frontiers in Microbiology Volume: 6 Pages: 1552-1552
  • DOI: 10.3389/fmicb.2015.01552
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Rab3a is required for virion production of murine leukemia virus (2017)
  • Author(s): Y. Kubo, M. Izumida, H. Hayashi
  • Organizer: 日本ウイルス学会学術集会
• [Presentation] Identification of novel host anti-HIV-1 factors that are induced by interferon gamma (2017)
  • Author(s): Y. Kubo, M. Izumida, H. Hayashi, T. Matsuyama
  • Organizer: Nagasaki-Singapore Medical Symposium
  • Int'l Joint Research / Invited
• [Presentation] Rab3a is required for virion production of murine leukemia virus (2017)
  • Author(s): M. Izumida, H. Hayashi, Y. Kubo
  • Organizer: International Workshop on Retroviral Pathogenesis
  • Int'l Joint Research
• [Presentation] Role of a samll GTP-binding protein, Rab3a, in the formation of HIV-1 virion (2016)
  • Author(s): Y.Kubo, M. Izumida, H. Masumoto, K. Yasui, H. Hayashi, T. Matsuyama
  • Organizer: 日本ウイルス学会学術集会
  • Place of Presentation: 札幌コンベンションセンター（北海道・札幌市）
  • Year and Date: 2016-10-23
• [Presentation] Identification of a CD63 binding protein and its role in HIV replication (2015)
  • Author(s): Y. Kubo, M. Izumida, H. Masumoto, K. Yasui, H. Hayashi, T. Matsuyama
  • Organizer: 第６３回日本ウイルス学会学術集会
  • Place of Presentation: 福岡国際会議場（福岡県、福岡市）
  • Year and Date: 2015-11-22
• [Presentation] Placenta formation by human endogenous retrovirus is inhibited by interferons. (2015)
  • Author(s): M. Izumida, Y. Kubo, H. Hayashi, K. Yasui, T. Matsuyama
  • Organizer: 第６３回日本ウイルス学会学術集会
  • Place of Presentation: 福岡国際会議場（福岡県、福岡市）
  • Year and Date: 2015-11-22