Regulation of HIV-1 restriction factor Apobec3G by mRNA export factor

• Project/Area Number: 24659224
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Immunology
• Research Institution: Kumamoto University
• Principal Investigator: SAKAGUCHI NOBUO 熊本大学, 生命科学研究部, 教授 (70192086)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 免疫学 / 感染 / RNA

Research Abstract

HIV-1 viruses cause the AIDS-associated disease symptoms during the long-term infection period. We found that mRNA export factor GANP is encapsidated into the virions as a host factor associated with cytidine deaminase APOBEC3G (A3G). GANP is involved in the HIV-1 mRNA export pathway under the Rev-dependent manner. GANP binds to HIV-1 genomic (g)RNA in the virion by regulating viral RNA metabolism. GANP directly interacts with A3G in T-cells, and the interaction is through a unique region of Gag protein involved in HIV-1 gRNA encapsidation. GANP efficiently promotes the A3G incorporation into the viral core and enhances the non-infectious viral production in the host. This knowledge would suggest the feasibility of developing the in-vivo vaccination procedure.

Research Products

• [Journal Article] GANP regulates the choice of DNA repair pathway by DNA-PKcs interaction in AID-dependent IgV region diversification (2014)
  • Author(s): Eid MMA, Maeda K, Almofty SA, Singh SK, Shimoda M, Sakaguchi N.
  • Journal Title: The Journal of Immunology Volume: 192(印刷中) Issue: 12 Pages: 5529-5539
  • DOI: 10.4049/jimmunol.1400021
  • Peer Reviewed / Open Access
• [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 Issue: 3 Pages: 623-635
  • DOI: 10.1002/stem.1580
  • Peer Reviewed
• [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 Issue: 3 Pages: e1003937-e1003937
  • DOI: 10.1371/journal.ppat.1003937
  • Peer Reviewed
• [Journal Article] Histopathological evaluation of the diversity of cells susceptible to H5N1 virulent avian influenza virus (2013)
  • Author(s): Ogiwara 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 Issue: 1 Pages: 171-183
  • DOI: 10.1016/j.ajpath.2013.10.004
  • Peer Reviewed / Open Access
• [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 Sci Volume: 104 Issue: 10 Pages: 1278-1284
  • DOI: 10.1111/cas.12222
  • 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 Issue: 11 Pages: e76753-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 Issue: 1 Pages: 562-562
  • 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 Issue: 12 Pages: 6030-6039
  • DOI: 10.4049/jimmunol.1302057
  • Peer Reviewed
• [Journal Article] GANP regulates recruitment ofAID to immunoglobulin variable regions bymodulating transcription and nucleosomeoccupancy (2013)
  • Author(s): Shailendra Kumar Singh, Kazuhiko Maeda(co-first author), Mohammed Mansour AbbasEid, Sarah Ameen Almofty, Masaya Ono,Phuong Pham, Myron F. Goodman, and NobuoSakaguchi
  • Journal Title: Nat. Commun Volume: 4 Issue: 1 Pages: 1830-1830
  • DOI: 10.1038/ncomms2823
  • Peer Reviewed
• [Journal Article] Lyn signaling to upregulate GANP is critical for the survival of high-affinity B cells in germinal centers of lymphoid organs (2012)
  • Author(s): Kuwahara K, Nakaya T, Phimsen S, Toda T, Kitabatake M, Kaji T, Takemori T, Watanabe T, Sakaguchi N
  • Journal Title: J. Immunol Volume: 189 Issue: 7 Pages: 3472-3479
  • DOI: 10.4049/jimmunol.1200649
  • Peer Reviewed
• [Journal Article] Transgenic overexpression of G5PR that is normally augmented in centrocytes impairsthe enrichment of high-affinity antigen-specific B cells, increases peritoneal B-1a cells, and induces autoimmunity in aged female mice (2012)
  • Author(s): hi H, Ohtsuji M, Tsurui H, Hirose S, and Sakaguchi N
  • Journal Title: J. Immunol Volume: 189 Issue: 3 Pages: 1193-1201
  • DOI: 10.4049/jimmunol.1102774
  • Peer Reviewed
• [Presentation] GANP interacts with APOBEC3G and facilitates its encapsidation into the virions to reduce HIV-1 infectivity (2014)
  • Author(s): Maeda K, Almofty SA, Singh SK, Eid MMA, Shimoda M, Ikeda T, Koito A, Pham P, Goodman MF, Sakaguchi N.
  • Organizer: Asian-African Research Forum on Emerging and Reemerging Infections 2014
  • Place of Presentation: 仙台国際センター(宮城)
  • Year and Date: 2014-01-20
• [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
• [Presentation] Role of mammalian TREX-2 component in HIV-1 mRNA export (2013)
  • Author(s): Almofty SA, Maeda K, Singh SK, Eid MMA, Shimoda M, Kawabata T, Sakaguchi N.
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ(千葉)
  • Year and Date: 2013-12-12
• [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、サーラアルモフティ、シェイレンドラシン、モハメドエイド、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・総会
  • 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(熊本)
  • Year and Date: 2013-11-21
• [Presentation] GANP regulates transcription and nucleosome occupancy at the immunoglobulin variable region for AID-accession (2013)
  • Author(s): Maeda K, Singh SK, Eid MMA, Almofty SA, Sakaguchi N.
  • Organizer: The 9th China-Japan Joint Laboratory Workshop : Pathogenesis, Gene Regulation and Signal Transduction
  • Place of Presentation: Chinese Academy of Sciences (北京、中国)
  • Year and Date: 2013-11-01
• [Presentation] Role of mammalian TREX-2 component GANP in HIV-1 infection (2013)
  • Author(s): Maeda K, Almofty SA, Shimoda M, Singh SK, Eid MMA, Kawabata T, Ikeda T, Shida H, Koito A, Sakaguchi N.
  • Organizer: 第14回熊本エイズセミナーGCOEジョイント国際シンポジウム
  • Place of Presentation: 熊本キャッスルホテル、阿蘇リゾートグランヴィリオホテル(熊本)
  • Year and Date: 2013-10-30
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [Presentation] GANP regulates APOBEC3G targeting for reduction of HIV-1 infectivity (2012)
  • Author(s): Singh SK, Maeda K, Eid MMA, Almofty SA, Shimoda M, Sakaguchi N.
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸国際会議場、神戸国際展示場、神戸ポートピアホテル(兵庫)
  • Year and Date: 2012-12-05
• [Presentation] Escorting APOBEC3G toward the full length HIV-1 mRNA at the cytoplasmic P bodies (2012)
  • Author(s): Almofty SA, Maeda K, Singh SK, Eid MMA, Shimoda M, Sakaguchi N.
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸国際会議場、神戸国際展示場、神戸ポートピアホテル(兵庫)
  • Year and Date: 2012-12-05
• [Presentation] GANPを介したAPOBEC3Gの抗HIV感染阻止機構の解析 (2012)
  • Author(s): 前田和彦、サーラアルモフティ、シェイレンドラシン、モハメドエイド、下田真唯子、池田輝政、小糸厚、阪口薫雄
  • Organizer: 第26回日本エイズ学会学術集会・総会
  • Place of Presentation: 慶応義塾大学、日吉キャンパス(神奈川)
  • Year and Date: 2012-11-25
• [Presentation] Mammalian TREX-2 component GANP is involved in HIV-1 mRNA export (2012)
  • Author(s): Maeda K, Almofty SA, Singh SK, Eid MMA, Shimoda M, Ikeda T, Shida H, Koito A, Pham P, Goodman MF, Sakaguchi N.
  • Organizer: 第13回熊本エイズセミナーGCOEジョイント国際シンポジウム
  • Place of Presentation: ホテル日航熊本、阿蘇リゾートグランヴィリオホテル(熊本)
  • Year and Date: 2012-10-26
• [Presentation] Mammalian TREX-2 component GANP is involved in HIV-1 mRNA export (2012)
  • Author(s): Kazuhiko Maeda
  • Organizer: The 13th Kumamoto AIDS Seminar GCOE Joint International Symposium
  • Place of Presentation: Hotel Nikko Kumamoto, Aso Resort Grandvrio Hotel
• [Presentation] GANPを介したAPOBEC3Gの抗HIV感染阻止機構の解析 (2012)
  • Author(s): 前田和彦
  • Organizer: 第26回日本エイズ学会学術集会・総会
  • Place of Presentation: 慶応義塾大学 日吉キャンパス
• [Presentation] GANP regulates transcription and nucleosome occupancy at the immunoglobulin variable region for AID-accession (2012)
  • Author(s): Kazuhiko Maeda
  • Organizer: The 41th Annual Meeting of the Japanese Society for Immunology
  • Place of Presentation: Kobe International Conference Center Kobe International Exhibition Hall Kobe Portopia Hotel
• [Presentation] Regulation of immunoglobulin variableregion diversification through GANP-mediated regulation of DNA double-strand break repair machinery (2012)
  • Author(s): Mohammed Mansour Abbas Eid
  • Organizer: The 41th Annual Meeting of the Japanese Society for Immunology
  • Place of Presentation: Kobe International Conference Center Kobe International Exhibition Hall Kobe Portopia Hotel
• [Presentation] Escorting APOBEC3G toward the fulllength HIV-1 mRNA at the cytoplasmic P bodies (2012)
  • Author(s): Sarah Ameen Almofty
  • Organizer: The 41th Annual Meeting of the Japanese Society for Immunology
  • Place of Presentation: Kobe International Conference Center Kobe International Exhibition Hall Kobe Portopia Hotel
• [Presentation] GANP regulates APOBEC3G targeting for reduction of HIV-1 infectivity (2012)
  • Author(s): Shailendra Kumar Singh
  • Organizer: The 41th Annual Meeting of the Japanese Society for Immunology
  • Place of Presentation: Kobe International Conference Center Kobe International Exhibition Hall Kobe Portopia Hotel
• [Book] 免疫グロブリンの体細胞高頻度突然変異誘導とGANP、臨床免疫・アレルギー科(61(5)) (2014)
  • Author(s): 下田真唯子、前田和彦、阪口薫雄
  • Publisher: 科学評論社
• [Book] 胚中心B細胞の高親和性成熟におけるGANPの役割、臨床免疫・アレルギー科(60(2)) (2013)
  • Author(s): 前田和彦、阪口薫雄
  • Publisher: 科学評論社
• [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
  • Publisher: 臨床免疫・アレルギー科 科学評論社
• [Book] B細胞の生存維持とmiRNA、臨床免疫・アレルギー科(58(3)) (2012)
  • Author(s): 前田和彦、阪口薫雄
  • Publisher: 科学評論社
• [Book] 免疫学コア講義改訂3版、編集、第6章、第9章、付表1 (2012)
  • Author(s): 阪口薫雄、前田和彦
  • Publisher: 南山堂
• [Book] 自己免疫疾患とB1細胞、臨床免疫・アレルギー科(57(2)) (2012)
  • Author(s): 北畠正大、阪口薫雄
  • Publisher: 科学評論社
• [Book] プロテインホスファターゼ2Aの調節と自己免疫、臨床免疫・アレルギー科(57(2)) (2012)
  • Author(s): 前田和彦、阪口薫雄
  • Publisher: 科学評論社
• [Remarks] 2013年12月17日、読売新聞、「エイズ治療につながる可能性」 新聞報道
• [Remarks] 2013年12月18日、熊本日日新聞、「タンパク質HIV破壊に貢献」 新聞報道
• [Remarks] 2013年12月19日、西日本新聞、「HIV感染力阻害酵素運び役の機能確認」 新聞報道
• [Remarks] 2013年12月16日、TBSテレビ、「朝ズバッ!」、RKK熊本放送「ニュースローカル」、NHK熊本放送局「クマロク!」 テレビ報道
• [Remarks]
  • URL: http://www.k-immu.jp/ja/