ｍＲＮＡ輸送因子ＧＡＮＰによるＨＩＶ―１感染阻止分子Ａｐｏｂｅｃ３Ｇ制御

2013 Fiscal Year Annual Research Report

• Project/Area Number: 24659224
• Research Institution: Kumamoto 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

• [Journal Article] Infection of adult thymus with murine retrovirus induces virus-specific central tolerance that prevents functional memory CD8+ T cell differentiation (2014)
  • 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 stability (2014)
  • 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 virus (2013)
  • 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 system (2013)
  • 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 survival (2013)
  • 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 infectivity (2013)
  • 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 cholangiocarcinoma (2013)
  • 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 diversification (2014)
  • 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 export (2013)
  • 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 diversification (2013)
  • 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-accession (2013)
  • 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 cells (2013)
  • 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 proliferation (2013)
  • 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 infection (2013)
  • 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