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Functional analysis of lipid domains in influenza virus infection with super-resolution microscopy

Research Project

Project/Area Number 15K07957
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Biological pharmacy
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

ABE MITSUHIRO  国立研究開発法人理化学研究所, 開拓研究本部, 専任研究員 (90415068)

Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsインフルエンザウイルス / フリップフロップ / 脂質ラフト / スフィンゴミエリン / PIP2 / 1分子イメージング / STORM / 脂質の非対称性 / インフルエンザ
Outline of Final Research Achievements

Analysis with a combination of lipid probes and super-resolution microscopy indicates that the influenza virus buds from the edges of the sphingomyelin(SM)/cholesterol(Chol) domains in MDCK cells. Several lines of evidence suggest that breakage of lipid asymmetry at the plasma membrane leads to the decrease of influenza virus proliferation. I screened for the factor involved in SM/Chol asymmetry at the plasma membrane. Immuno-electron microscopy with sodium dodecyl sulfate (SDS)-treated freeze-fracture replica labeling (SDS-FRL) indicates that the domains of phosphatidylinositol 4,5-bisphosphate (PIP2) increase in the inner leaflet of the plasma membrane. These results suggest that the stability of domains of PIP2 increases the influenza virus proliferation in mammalian cells.

Academic Significance and Societal Importance of the Research Achievements

本研究により、宿主側の細胞膜における脂質の非対称性は、インフルエンザウイルスの増殖・拡散に関わっていることが示唆された。同様の現象が、ほかのウイルスでも見られることが十分期待される。ウイルスは変異しやすく、構成タンパク質の分類上における種類の多さから、ウイルスそのものを標的とする薬剤の開発は難しい。本申請課題での結果を基に、ホスト側の因子を標的とした薬剤で、脂質の非対称性を不安定にし、ウイルスの感染効率が低下するものがあれば、ウイルスの増殖・拡散に対する薬剤の開発を容易に行えることが期待される。

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (15 results)

All 2018 2017 2016 2015 Other

All Int'l Joint Research (1 results) Journal Article (11 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 11 results,  Open Access: 10 results,  Acknowledgement Compliant: 5 results) Presentation (1 results) Remarks (2 results)

  • [Int'l Joint Research] CNRS/Faculte de Pharmacie/Universite de Strasbourg(フランス)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Single-molecule diffusion-based estimation of ligand effects on G protein?coupled receptors2018

    • Author(s)
      Yanagawa Masataka、Hiroshima Michio、Togashi Yuichi、Abe Mitsuhiro、Yamashita Takahiro、Shichida Yoshinori、Murata Masayuki、Ueda Masahiro、Sako Yasushi
    • Journal Title

      Science Signaling

      Volume: 11 Issue: 548 Pages: 1-16

    • DOI

      10.1126/scisignal.aao1917

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mutation-Specific Mechanisms of Hyperactivation of Noonan Syndrome SOS Molecules Detected with Single-molecule Imaging in Living Cells2017

    • Author(s)
      Nakamura Yuki、Umeki Nobuhisa、Abe Mitsuhiro、Sako Yasushi
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 1-10

    • DOI

      10.1038/s41598-017-14190-6

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Raft-based sphingomyelin interactions revealed by new fluorescent sphingomyelin analogs2017

    • Author(s)
      Masanao Kinoshita, Kenichi GN Suzuki, Nobuaki Matsumori, Misa Takada, Hikaru Ano, Kenichi Morigaki, Mitsuhiro Abe, Asami Makino, Toshihide Kobayashi, Koichiro M Hirosawa, Takahiro K Fujiwara, Akihiro Kusumi, Michio Murata
    • Journal Title

      J Cell Biol

      Volume: 未定 Issue: 4 Pages: 1183-1204

    • DOI

      10.1083/jcb.201607086

    • NAID

      120005998045

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Dynamics of sphingomyelin- and cholesterol-enriched lipid domains during cytokinesis2017

    • Author(s)
      Abe M, Kobayashi T.
    • Journal Title

      Methods in Cell Biology

      Volume: 137 Pages: 15-24

    • DOI

      10.1016/bs.mcb.2016.03.030

    • ISBN
      9780128096734
    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Psychosine-triggered endomitosis is modulated by membrane sphingolipids through regulation of phosphoinositide 4,5-bisphosphate production at the cleavage furrow.2016

    • Author(s)
      Watanabe H, Okahara K, Naito-Matsui Y, Abe M, Go S, Inokuchi J, Okazaki T,Kobayashi T, Kozutsumi Y, Oka S, Takematsu H.
    • Journal Title

      Mol Biol Cell.

      Volume: 27 Issue: 13 Pages: 2037-2050

    • DOI

      10.1091/mbc.e15-08-0555

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Phospholipase Cβ1 induces membrane tubulation and is involved in caveolae formation.2016

    • Author(s)
      Inaba T, Kishimoto T, Murate M, Tajima T, Sakai S, Abe M, Makino A, Tomishige N, Ishitsuka R, Ikeda Y, Takeoka S, Kobayashi T.
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: 113 Issue: 28 Pages: 7834-7839

    • DOI

      10.1073/pnas.1603513113

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] A novel spingomyeling/cholesterol specific probe reveals the dynamics of the membrane domain during virus and in Nieman-Pick type C2016

    • Author(s)
      Makino, A., Sako, Y. et al.
    • Journal Title

      FASEB J.

      Volume: 31 Issue: 4 Pages: 1301-1322

    • DOI

      10.1096/fj.201500075r

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Acute accumulation of free cholesterol induces the degradation of perilipin 2 and Rab18-dependent fusion of ER and lipid droplets in cultured human hepatocytes.2016

    • Author(s)
      Makino A, Hullin-Matsuda F, Murate M, Abe M, Tomishige N, Fukuda M, Yamashita S, Fujimoto T, Vidal H, Lagarde M, Delton I, Kobayashi T.
    • Journal Title

      Mol Biol Cell

      Volume: 27 Issue: 21 Pages: 3293-3304

    • DOI

      10.1091/mbc.e15-10-0730

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Zds1/Zds2-PP2ACdc55 complex specifies signaling output from Rho1 GTPase2016

    • Author(s)
      Jonasson EM, Rossio V, Hatakeyama R, Abe M, Ohya Y, Yoshida S
    • Journal Title

      J Cell Biol

      Volume: 212(1) Issue: 1 Pages: 51-61

    • DOI

      10.1083/jcb.201508119

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Evaluation of aegerolysins as novel tools to detect and visualize ceramide phosphoethanolamine, a major sphingolipid in invertebrates2015

    • Author(s)
      Bhat HB, Ishitsuka R, Inaba T, Murate M, Abe M, Makino A, Kohyama-Koganeya A, Nagao K, Kurahashi A, Kishimoto T, Tahara M, Yamano A, Nagamune K, Hirabayashi Y, Juni N, Umeda M, Fujimori F, Nishibori K, Yamaji-Hasegawa A, Greimel P, Kobayashi T.
    • Journal Title

      FASEB J

      Volume: 29(9) Issue: 9 Pages: 3920-34

    • DOI

      10.1096/fj.15-272112

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Transbilayer distribution of lipids at nano scale.2015

    • Author(s)
      Murate M, Abe M, Kasahara K, Iwabuchi K, Umeda M, Kobayashi T
    • Journal Title

      J Cell Sci

      Volume: 128 Pages: 1627-1638

    • DOI

      10.1242/jcs.163105

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 脂質イメージングによる脂質ラフトの解析2016

    • Author(s)
      阿部充宏
    • Organizer
      第42回レーザ顕微鏡研究会講演会
    • Place of Presentation
      理化学研究所 和光事業所 (埼玉県和光市)
    • Year and Date
      2016-07-07
    • Related Report
      2016 Research-status Report
  • [Remarks] 細胞膜の受容体1分子の動きから薬効を評価

    • URL

      http://www.riken.jp/pr/press/2018/20180919_1/

    • Related Report
      2018 Annual Research Report
  • [Remarks] マイタケ由来タンパク質がインフルエンザウイルスの増殖を抑制

    • URL

      http://www.riken.jp/pr/press/2016/20160822_2/

    • Related Report
      2016 Research-status Report

URL: 

Published: 2015-04-16   Modified: 2020-03-30  

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