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2013 Fiscal Year Annual Research Report

mRNA輸送因子GANPによるHIV―1感染阻止分子Apobec3G制御

Research Project

Project/Area Number 24659224
Research InstitutionKumamoto University

Principal Investigator

阪口 薫雄  熊本大学, 生命科学研究部, 教授 (70192086)

Keywords免疫学 / 感染 / RNA
Research Abstract

HIV感染は免疫応答の破綻を引き起こしつつ病態を進行させる。mRNA核外輸送分子GANP は、HIV-1粒子に能動的に侵入する宿主因子であることを見いだした。GANPはHIV-1ゲノム(g)RNAと結合し、その代謝経路を制御し、ウイルス粒子に取り込まれると考えられる。 これまでにGANPはAPOBEC3G(A3G)と直接結合し、ウイルス粒子への取り込みを制御していることを見いだしている。このことは、GANPがA3Gの機能を制御し、感染能力の無い「 不活性型ウイルス」の産生を促し、生体内ワクチンとして作用し免疫反応を高める効果を示すと考えられる。そしてウイルス粒子内への取り込み経路にはHIV-1 Gagのが必要である。最終年度は、GANPとA3Gがウイルス粒子に取り込まれる経路について詳細に解析を進めた。その結果、GANPとA3GがHIV-1 Gagタンパク質の異なる部位を介して取り込まれること、GANPの存在によって効率よくA3Gがウイルス粒子内に取り込まれることをしめした。以上の結果は、HIV-1のmRNA輸送経路においてGANPが非スプライス型の全長HIV-1gRNAのRev依存性核外輸送を促進し細胞質内、ウイルス粒子内でHIV-1 gRNAと結合することと密接に関連することを裏付けている。

  • Research Products

    (18 results)

All 2014 2013

All Journal Article (7 results) (of which Peer Reviewed: 7 results) Presentation (10 results) Book (1 results)

  • [Journal Article] Infection of adult thymus with murine retrovirus induces virus-specific central tolerance that prevents functional memory CD8+ T cell differentiation2014

    • Author(s)
      Takamura S, Kajiwara E, Tsuji-Kawahara S, Masumoto T, Fujisawa M, Kato M, Chikaishi T, Kawasaki Y, Kinoshita S, Itoi M, Sakaguchi N, Miyazawa M.
    • Journal Title

      PLoS Pathog

      Volume: 10 Pages: e1003937

    • DOI

      10.1371/journal.ppat.1003937

    • Peer Reviewed
  • [Journal Article] Pcid2 inactivates developmental genes in human and mouse embryonic stem cells to sustain their pluripotency by modulation of EID1 stability2014

    • Author(s)
      Ye, B., Dai, Z., Liu, B., Wang, R., Li, C., Huang, G., Wang, S., Xia, P., Yang, X., Kuwahara, K., Sakaguchi, N., Fan, Z.
    • Journal Title

      Stem Cells

      Volume: 32 Pages: 623-635

    • DOI

      10.1002/stem.1580

    • Peer Reviewed
  • [Journal Article] Histopathological evaluation of the diversity of cells susceptible to H5N1 virulent avian influenza virus2013

    • Author(s)
      O giwara H, Yasui F, Munekata K, Takagi-Kamiya A, Munakata T, Nomura N, Shibasaki F, Kuwahara K, Sakaguchi N, Sakoda Y, Kida H, Kohara M.
    • Journal Title

      Am. J. Pathol

      Volume: 184 Pages: 171-183

    • DOI

      10.1016/j.ajpath.2013.10.004

    • Peer Reviewed
  • [Journal Article] Broad-spectrum detection of h5 subtype influenza a viruses with a new fluorescent immunochromatography system2013

    • Author(s)
      Sakurai A, Takayama K, Nomura N, Munakata T, Yamamoto N, Tamura T, Yamada J, Hashimoto M, Kuwahara K, Sakoda Y, Suda Y, Kobayashi Y, Sakaguchi N, Kida H, Kohara M, Shibasaki F.
    • Journal Title

      PLoS One

      Volume: 8 Pages: e76753

    • DOI

      10.1371/journal.pone.0076753

    • Peer Reviewed
  • [Journal Article] Breast cancers with high DSS1 expression that potentially maintains BRCA2 stability have poor prognosis in the relapse-free survival2013

    • Author(s)
      Rezano A, Kuwahara K, Yamamoto-Ibusuki M, Kitabatake M, Moolthiya P, Phimsen S, Suda T, Tone S, Yamamoto Y, Iwase H, Sakaguchi N.
    • Journal Title

      BMC Cancer

      Volume: 13 Pages: 562

    • DOI

      10.1186/1471-2407-13-562

    • Peer Reviewed
  • [Journal Article] GANP interacts with APOBEC3G and facilitates its encapsidation into the virions to reduce HIV-1 infectivity2013

    • Author(s)
      Maeda K, Almofty SA (co-first author), Singh SK, Eid MMA, Shimoda M, Ikeda T, Koito A, Pham P, Goodman MF, Sakaguchi N.
    • Journal Title

      J. Immunol

      Volume: 191 Pages: 6030-6039

    • DOI

      10.4049/jimmunol.1302057

    • Peer Reviewed
  • [Journal Article] CA-S27: a novel Lewis a associated carbohydrate epitope is diagnostic and prognostic for cholangiocarcinoma2013

    • Author(s)
      Silsirivanit, A., Araki, N., Wongkham, C., Vaeteewoottacharn, K., Pairojkul, C., Kuwahara, K., Narimatsu, Y., Sawaki, H., Narimatsu, H., Okada, S., Sakaguchi, N., Wongkham, S.
    • Journal Title

      Cancer Science

      Volume: 104 Pages: 1278-1284

    • DOI

      10.1111/cas.12222

    • Peer Reviewed
  • [Presentation] GANP plays a regulatory role in the choice of DNA repair pathway by dissociating DNA-PKcs in AID-induced immunoglobulin V-region diversification2014

    • Author(s)
      Sakaguchi, N., Eid, M. M. A., Singh, S. K., Almofty, S. A., Shimoda, M, Maeda, K.
    • Organizer
      Keystone Symposia Conference Biology of B Cell Responses
    • Place of Presentation
      Keystone, Colorado, USA
    • Year and Date
      20140209-20140214
  • [Presentation] Role of mammalian TREX-2 component in HIV-1 mRNA export2013

    • Author(s)
      Almofty, S. A., Maeda, K., Singh, S. K., Eid, M. M. A., Shimoda, M., Kawabata, T., Sakaguchi, N.
    • Organizer
      The 42th Annual Meeting of the Japanese Society for Immunology
    • Place of Presentation
      Makuhari Messe
    • Year and Date
      20131211-20131213
  • [Presentation] B cell-associated regulation of DNA repair pathway through interaction with DNA-PKcs in IgV-region diversification2013

    • Author(s)
      Eid, M. M. A., Maeda, K., Almofty, S. A., Singh, S. K., Shimoda, M., Sakaguchi, N.
    • Organizer
      The 42th Annual Meeting of the Japanese Society for Immunology
    • Place of Presentation
      Makuhari Messe
    • Year and Date
      20131211-20131213
  • [Presentation] GANP regulates transcription and nucleosome occupancy at the immunoglobulin variable region for AID-accession2013

    • Author(s)
      Maeda, K., Singh, S. K., Eid, M. M. A., Almofty, S. A., Shimoda, M., Kawabata, T., Sakaguchi, N.
    • Organizer
      The 42th Annual Meeting of the Japanese Society for Immunology
    • Place of Presentation
      Makuhari Messe
    • Year and Date
      20131211-20131213
  • [Presentation] Protein phosphatase subunit G5PR regulates the plasma blast differentiation and autoantibody production of peritoneal B-1a cells2013

    • Author(s)
      Kitabatake, M., Zhang, T. L., Kuwahara K., Sakaguchi, N.
    • Organizer
      The 42th Annual Meeting of the Japanese Society for Immunology
    • Place of Presentation
      Makuhari Messe
    • Year and Date
      20131211-20131213
  • [Presentation] Mammalian Leng8 carrying a Sac3/GANP homologous region unregulated in germinal center B cells is involved in regulation of BCR-mediated proliferation2013

    • Author(s)
      Kuwahara, K., Kitabatake, M., Kitamura, D., Sakaguchi, N.
    • Organizer
      The 42th Annual Meeting of the Japanese Society for Immunology
    • Place of Presentation
      Makuhari Messe
    • Year and Date
      20131211-20131213
  • [Presentation] HIV感染経路における宿主因子GANPの役割2013

    • Author(s)
      前田和彦, アルモフティ・サーラ アミーン, シン・シャイレンドラ クマール, エイド・モハメド アバス, 下田真唯子, 川畑輝弥, 阪口薫雄
    • Organizer
      第27回日本エイズ学会学術集会
    • Place of Presentation
      市民会館崇城大学ホール(熊本市民会館)、熊本市国際交流会館民会館崇城大学ホール(熊本市民会館)、熊本市国際交流会館
    • Year and Date
      20131120-20131122
  • [Presentation] Role of mammalian TREX-2 component GANP in HIV-1 infection2013

    • Author(s)
      Maeda, K., Almofty, S. A., Shimoda, M., Singh, S. K., Eid, M. M. A., Kawabata, T., Ikeda, T., Shida, H., Koito, A., Sakaguchi, N.
    • Organizer
      The 14th Kumamoto AIDS Seminar GCOE Joint International Symposium
    • Place of Presentation
      Kumamoto Castle Hotel, Aso Resort Grandvrio Hotel
    • Year and Date
      20131029-20131031
  • [Presentation] 乳癌発症における TREX2 複合体の役割2013

    • Author(s)
      桑原 一彦、岩瀬 弘敬、阪口 薫雄
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      20131003-20131005
  • [Presentation] 乳癌発症におけるmRNA核外輸送複合体分子GANP異常の関与2013

    • Author(s)
      桑原 一彦、阪口 薫雄
    • Organizer
      第17回日本がん分子標的治療学会学術集会
    • Place of Presentation
      国立京都国際会館立京都国際会館
    • Year and Date
      20130612-20130614
  • [Book] 胚中心B細胞の高親和性成熟におけるGANPの役割2013

    • Author(s)
      前田和彦、阪口薫雄
    • Total Pages
      (60) p115-121
    • Publisher
      臨床免疫・アレルギー科 科学評論社

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Published: 2015-05-28  

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