• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Research of novel treatments for severe influenza by controlling host factors

Research Project

Project/Area Number 21H02376
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 42030:Animal life science-related
Research InstitutionHokkaido University

Principal Investigator

Ohno Marumi  北海道大学, 人獣共通感染症国際共同研究所, 助教 (50794202)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥13,000,000 (Direct Cost: ¥10,000,000、Indirect Cost: ¥3,000,000)
Fiscal Year 2023: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Keywordsインフルエンザ / 宿主応答 / LOX-1 / 宿主因子 / 脂質代謝 / 血液凝固異常 / ウイルス感染症 / 生体応答 / エネルギー代謝障害
Outline of Research at the Start

毎年冬季に流行する季節性インフルエンザは、小児と高齢者を中心に世界中で年間およそ50万人を死に至らしめている。ウイルス感染に対する生体応答の結果引き起こされるエネルギー代謝障害と血液凝固異常が重症化に関わる重要なファクターであると我々のこれまでの研究から示唆されている。本研究は、インフルエンザにおいてエネルギー代謝障害と血液凝固異常が引き起こされるメカニズムを解明し、これらをコントロールすることでインフルエンザ及びその他の感染症の重症化を防ぐ新たな治療方法の確立を目指すものである。

Outline of Final Research Achievements

In this study, detailed analysis of the host biological response to influenza virus infection has been conducted in mice. Interestingly, lectin-like oxidized LDL receptor-1 (LOX-1) was shown to be required for blood coagulation abnormalities that occur during severe influenza and also for proper regulation of immune cell responses and repair of damaged lung tissue. Oxidized phospholipids, which have been demonstrated to increase with infection with various pathogens, were also suggested to contribute to the elimination of viruses and dying cells via the promotion of programed cell death and phagocytosis of infected cells.
These findings indicate that regulatory systems of host lipid metabolism and lipid quality are potential new therapeutic targets in viral infections.

Academic Significance and Societal Importance of the Research Achievements

マウスを用いた実験から、宿主の脂質代謝や脂質クオリティの制御システムがインフルエンザの病原性を左右すると明らかになった。本研究で観察されたものと共通する血中脂質プロファイルの変化がすでに新型コロナウイルス感染症やデング熱ウイルス感染症患者で報告されている。ウイルス自体ではなく宿主に重篤な症状を引き起こす生体応答をコントロールすることで重症化を防ぐという考え方が近年広がりつつある。ここで示された脂質制御に関わる生体応答は広くウイルス感染症における治療標的となりうると期待される。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • Research Products

    (19 results)

All 2024 2023 2022 2021

All Journal Article (15 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 15 results,  Open Access: 7 results) Presentation (4 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Increased expression of CD38 on endothelial cells in SARS-CoV-2 infection in cynomolgus macaques2024

    • Author(s)
      Nguyen Cong Thanh、Nakayama Misako、Ishigaki Hirohito、Kitagawa Yoshinori、Kakino Akemi、Ohno Marumi、Shingai Masashi、Suzuki Yasuhiko、Sawamura Tatsuya、Kida Hiroshi、Itoh Yasushi
    • Journal Title

      Virology

      Volume: 594 Pages: 110052-110052

    • DOI

      10.1016/j.virol.2024.110052

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Extraction of the CDRH3 sequence of the mouse antibody repertoire selected upon influenza virus infection by subtraction of the background antibody repertoire2024

    • Author(s)
      Shingai Masashi、Iida Sayaka、Kawai Naoko、Kawahara Mamiko、Sekiya Toshiki、Ohno Marumi、Nomura Naoki、Handabile Chimuka、Kawakita Tomomi、Omori Ryosuke、Yamagishi Junya、Sano Kaori、Ainai Akira、Suzuki Tadaki、Ohnishi Kazuo、Ito Kimihito、Kida Hiroshi
    • Journal Title

      Journal of Virology

      Volume: 98 Issue: 3

    • DOI

      10.1128/jvi.01995-23

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The elucidation of plasma lipidome profiles during severe influenza in a mouse model2023

    • Author(s)
      Ohno Marumi、Gowda Siddabasave Gowda B.、Sekiya Toshiki、Nomura Naoki、Shingai Masashi、Hui Shu-Ping、Kida Hiroshi
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 14210-14210

    • DOI

      10.1038/s41598-023-41055-y

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Assessing the pyrogenicity of whole influenza virus particle vaccine in cynomolgus macaques2023

    • Author(s)
      Ohno Marumi、Sagata Masataka、Sekiya Toshiki、Nomura Naoki、Shingai Masashi、Endo Masafumi、Kimachi Kazuhiko、Suzuki Saori、Thanh Nguyen Cong、Nakayama Misako、Ishigaki Hirohito、Ogasawara Kazumasa、Itoh Yasushi、Kino Yoichiro、Kida Hiroshi
    • Journal Title

      Vaccine

      Volume: 41 Issue: 3 Pages: 787-794

    • DOI

      10.1016/j.vaccine.2022.12.020

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inactivated Whole Virus Particle Influenza Vaccine Induces Anti-Neuraminidase Antibodies That May Contribute to Cross-Protection against Heterologous Virus Infection2022

    • Author(s)
      Handabile Chimuka、Sekiya Toshiki、Nomura Naoki、Ohno Marumi、Kawakita Tomomi、Shingai Masashi、Kida Hiroshi
    • Journal Title

      Vaccines

      Volume: 10 Issue: 5 Pages: 804-804

    • DOI

      10.3390/vaccines10050804

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inactivated whole influenza virus particle vaccines induce neutralizing antibodies with an increase in immunoglobulin gene subclones of B-lymphocytes in cynomolgus macaques2022

    • Author(s)
      Shiohara M、Suzuki Saori、Shichinohe S、Ishigaki H、Nakayama M、Nomura N、Shingai M、Sekiya T、Ohno M、Iida S、Kawai N、Kawahara M、Yamagishi J、Ito K、Mitsumata R、Ikeda T、Motokawa K、Sobue T、Kida H、Ogasawara K、Itoh Y
    • Journal Title

      Vaccine

      Volume: 40 Issue: 30 Pages: 4026-4037

    • DOI

      10.1016/j.vaccine.2022.05.045

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Determination of short-chain fatty acids by N,N-dimethylethylenediamine derivatization combined with liquid chromatography/mass spectrometry and their implication in influenza virus infection2022

    • Author(s)
      Gowda Divyavani、Li Yonghan、B Gowda Siddabasave Gowda、Ohno Marumi、Chiba Hitoshi、Hui Shu-Ping
    • Journal Title

      Analytical and Bioanalytical Chemistry

      Volume: 414 Issue: 22 Pages: 6419-6430

    • DOI

      10.1007/s00216-022-04217-x

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Immunization with inactivated whole virus particle influenza virus vaccines improves the humoral response landscape in cynomolgus macaques2022

    • Author(s)
      Chua BY、Sekiya T、Koutsakos M、Nomura N、Rowntree LC、Nguyen THO、McQuilten HA、Ohno M、Ohara Y、Nishimura T、Endo M、Itoh Y、Habel JR、Selva KJ、Wheatley AK、Wines BD、Hogarth PM、Kent SJ、Chung AW、Jackson DC、Brown LE、Shingai M、Kedzierska K、Kida H
    • Journal Title

      PLOS Pathogens

      Volume: 18 Issue: 10 Pages: e1010891-e1010891

    • DOI

      10.1371/journal.ppat.1010891

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Updating the influenza virus library at Hokkaido University -It's potential for the use of pandemic vaccine strain candidates and diagnosis2021

    • Author(s)
      Nomura Naoki、Matsuno Keita、Shingai Masashi、Ohno Marumi、Sekiya Toshiki、Omori Ryosuke、Sakoda Yoshihiro、Webster Robert G.、Kida Hiroshi
    • Journal Title

      Virology

      Volume: 557 Pages: 55-61

    • DOI

      10.1016/j.virol.2021.02.005

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Selecting and Using the Appropriate Influenza Vaccine for Each Individual2021

    • Author(s)
      Sekiya Toshiki、Ohno Marumi、Nomura Naoki、Handabile Chimuka、Shingai Masashi、Jackson David C.、Brown Lorena E.、Kida Hiroshi
    • Journal Title

      Viruses

      Volume: 13 Issue: 6 Pages: 971-971

    • DOI

      10.3390/v13060971

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Potent priming by inactivated whole influenza virus particle vaccines is linked to viral RNA uptake into antigen presenting cells2021

    • Author(s)
      Shingai Masashi、Nomura Naoki、Sekiya Toshiki、Ohno Marumi、et al.,
    • Journal Title

      Vaccine

      Volume: 39 Issue: 29 Pages: 3940-3951

    • DOI

      10.1016/j.vaccine.2021.05.065

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Detection and Structural Characterization of SFAHFA Homologous Series in Mouse Colon Contents by LTQ-Orbitrap-MS and Their Implication in Influenza Virus Infection2021

    • Author(s)
      B. Gowda Siddabasave Gowda、Gowda Divyavani、Ohno Marumi、Liang Chongsheng、Chiba Hitoshi、Hui Shu-Ping
    • Journal Title

      Journal of the American Society for Mass Spectrometry

      Volume: 32 Issue: 8 Pages: 2196-2205

    • DOI

      10.1021/jasms.1c00138

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Critical role of oxidized LDL receptor-1 in intravascular thrombosis in a severe influenza mouse model2021

    • Author(s)
      Ohno Marumi、Kakino Akemi、Sekiya Toshiki、Nomura Naoki、Shingai Masashi、Sawamura Tatsuya、Kida Hiroshi
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1

    • DOI

      10.1038/s41598-021-95046-y

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Defining the kinetic effects of infection with influenza virus A/PR8/34 (H1N1) on sphingosine-1-phosphate signaling in mice by targeted LC/MS2021

    • Author(s)
      Gowda Divyavani、Ohno Marumi、B. Gowda Siddabasave Gowda、Chiba Hitoshi、Shingai Masashi、Kida Hiroshi、Hui Shu-Ping
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 20161-20161

    • DOI

      10.1038/s41598-021-99765-0

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Abnormal Blood Coagulation and Kidney Damage in Aged Hamsters Infected with Severe Acute Respiratory Syndrome Coronavirus 22021

    • Author(s)
      Ohno Marumi、Sasaki Michihito、Orba Yasuko、Sekiya Toshiki、Masum Md. Abdul、Ichii Osamu、Sawamura Tatsuya、Kakino Akemi、Suzuki Yasuhiko、Kida Hiroshi、Sawa Hirofumi、Shingai Masashi
    • Journal Title

      Viruses

      Volume: 13 Issue: 11 Pages: 2137-2137

    • DOI

      10.3390/v13112137

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 重症インフルエンザにおけるリン脂質の代謝異常とその生理学的意義2023

    • Author(s)
      大野円実
    • Organizer
      第34回日本生体防御学会学術総会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Characteristic lipid profiles in severe influenza2022

    • Author(s)
      Marumi Ohno, Siddabasave Gowda B. Gowda, Masashi Shingai, Hiroshi Kida
    • Organizer
      第69回日本ウイルス学会学術集会
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] カニクイザルにおける不活化インフルエンザウイルス全粒子ワクチンの発熱源性の解析2022

    • Author(s)
      大野円実、佐潟雅隆、遠藤昌史、鈴木紗織、伊藤靖、新開大史、喜田宏
    • Organizer
      第26回日本ワクチン学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Influenza virus infection causes disorder of energy metabolism and blood coagulation.2021

    • Author(s)
      Marumi Ohno
    • Organizer
      BioST2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research

URL: 

Published: 2021-04-28   Modified: 2025-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi