Development of novel therapy against the transcriptional regulatory mechanism of human immunodeficiency virus(HIV).

• Project/Area Number: 21390142
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Virology
• Research Institution: Nagoya City University
• Principal Investigator: OKAMOTO Takashi 名古屋市立大学, 大学院・医学研究科, 教授 (40146600)
• Co-Investigator(Kenkyū-buntansha): ASAMITSU Kaori 名古屋市立大学, 大学院・医学研究科, 講師 (20381783)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000); Fiscal Year 2011: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2010: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2009: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
• Keywords: HIV-1 / NF-κB / Tat / Cyclin T1 / 潜伏感染 / HDAC / クロマチン / HIV / 転写機構

Research Abstract

In this study, we have been exploring the step of viral transcription that is the rate-determining step of viral replication in order to provide vital information for the development of novel anti-HIV strategy. We have clarified the interaction between Tat and CycT1 at the AA side chain level by creating a number of CycT1 mutants in which critical AA resides were substituted by Ala based recently published 3D structure of Tat-CycT1 molecular complex. These findings have provided scientific basis for the development of Tat inhibitors.

Research Products

• [Journal Article] Microbial Interaction of Periodontopathic Bacterium Porphyromonas gingivalis and HIV-Possible Causal Link of Periodontal Diseases to AIDS Progression (2012)
  • Author(s): Imai K, Victoriano AF, Ochiai K, Okamoto T
  • Journal Title: Curr HIV Res Volume: (In press)
  • Peer Reviewed
• [Journal Article] Cytokinin dehydrogenase differentially regulates cytokinin and indirectly affects hydrogen peroxide accumulation in tomato leaf (2012)
  • Author(s): Cueno ME, Imai K, Ochiai K, Okamoto T
  • Journal Title: J Plant Physiol Volume: (In press)
  • Peer Reviewed
• [Journal Article] Reactivation of latent HIV-1 by a wide variety of butyric acid-producing bacteria (2012)
  • Author(s): Imai K, Yamada K, Tamura M, Ochiai K, Okamoto T
  • Journal Title: CeU Mol Life Sci Volume: (In press)
  • Peer Reviewed
• [Journal Article] Transcriptional control of HIV replication by multiple modulators and their implication for a novel anti-viral therapy (2011)
  • Author(s): Victoriano AF and Okamoto T
  • Journal Title: AIDS Res Hum Retroviruses Volume: 28 Pages: 125-38
  • Peer Reviewed
• [Journal Article] Positive and negative regulation of transcription from HIV provirus (2011)
  • Author(s): Okamoto T
  • Journal Title: Uirusu Volume: 61 Pages: 81-89
  • NAID: 10029357435
  • Peer Reviewed
• [Journal Article] Functional characterization of human cyclin T1 N-terminal region for human immunodeficiency virus-1 Tat transcriptional activation (2011)
  • Author(s): Asamitsu K, Hibi Y, Imai K, Victoriano AF, Kurimoto E, Kato K, Okamoto T
  • Journal Title: J Mol Biol Volume: 410 Pages: 887-895
  • URL: http://www.sciencedirect.com/science/article/pii/S0022283611004943
  • Peer Reviewed
• [Journal Article] Evaluation of online miRNA resources for biomedical applications (2011)
  • Author(s): Tan Gana NH, Victoriano AF, Okamoto T
  • Journal Title: Genes Cells Volume: 17 Issue: 1 Pages: 11-27
  • DOI: 10.1111/j.1365-2443.2011.01564.x
  • Peer Reviewed
• [Journal Article] Transcriptional control of HIV replication by multiple modulators and their implication for a novel anti-viral therapy (2011)
  • Author(s): Victoriano AF, Okamoto T
  • Journal Title: AIDS Res Hum Retroviruses Volume: 28 Issue: 2 Pages: 125-138
  • DOI: 10.1089/aid.2011.0263
  • Peer Reviewed
• [Journal Article] Protecting skin photoaging by NF-kB inhibitor (2010)
  • Author(s): Kiyotaka Tanaka, Kaori Asamitsu, Hiroaki Uranishi, Arunasiri Iddamalgoda, Kenichi Ito, Hiroyuki Kojima, Takashi Okamoto
  • Journal Title: Curr Drug Metab. Volume: 11 Pages: 431-435
  • Peer Reviewed
• [Journal Article] A-kinase interacting protein 1(AKIP1)acts as a molecular determinant of PKA in NF-kB signaling (2010)
  • Author(s): Nan Gao, Yurina Hibi, Marni Cueno, Kaori Asamitsu, Takashi Okamoto
  • Journal Title: J.Biol.Chem. Volume: 285 Pages: 28097-28104
  • Peer Reviewed
• [Journal Article] Molecular Mechanisms of HIV-1 Latency and Its Breakdown by Periodontal Diseases (2010)
  • Author(s): Kenichi Imai, Takashi Okamoto, Kuniyasu Ochiai
  • Journal Title: J.Oral Bioscience Volume: 52 Pages: 260-267
  • NAID: 10027106213
  • Peer Reviewed
• [Journal Article] Novel histone deacetylase inhibitor NCH-51 activates latent HIV-1 gene expression (2010)
  • Author(s): Ann Florence B Victoriano, Hiraaki Togami, Takaharu Ueno, Kaori Asamitsu, Takayoshi Suzuki, Naoki Miyata, Kuniyasu Ochiai, Takashi Okamoto
  • Journal Title: FEBS Letters Volume: 585 Pages: 1103-1111
  • Peer Reviewed
• [Journal Article] Preferential expression and immunogenicity of HIV-1 Tat fusion protein expressed in tomato plant (2010)
  • Author(s): Marni E.Cueno, Yurina Hibi, Katsuo Karamatsu, Yasuhiro Yasutomi, Kenichi Imai, Antonio C.Laurena, Takashi Okamoto
  • Journal Title: Transgenic.Res. (in press)
  • Peer Reviewed
• [Journal Article] Impaired plant growth and development caused by human immunodeficiency virus type 1 Tat (2010)
  • Author(s): Marni E.Cueno, Yurina Hibi, Kenichi Imai, Antonio C.Laurena, Takashi Okamoto
  • Journal Title: Transgenic.Res. (in press)
  • Peer Reviewed
• [Journal Article] Phosphoinositide 3-kinase inhibitor(wortmannin)inhibits pancreatic cancer cell motility and migration induced by hyaluronan in vitro and peritoneal metastatis in vivo (2009)
  • Author(s): Futoshi Teranishi, Naoko Takahashi, Nan Gao, Yoshimi Akamo, Hiromitsu Takeyama, Tadao Manabe, Takashi Okamoto
  • Journal Title: Cancer Science 100 Pages: 770-777
  • Peer Reviewed
• [Journal Article] Reactivation of latent HIV-1 infection by the periodontopathic bacterium Porphyromonas gingivalis involves histone modification (2009)
  • Author(s): Kenichi Imai, Kuniyasu Ochiai, Takashi Okamoto
  • Journal Title: J.Immunol. 182 Pages: 3688-95
  • NAID: 130004570886
  • Peer Reviewed
• [Journal Article] Follicular Dendritic Cells Activate HIV-1 Replication in Monocytes/Macrophages Through a Juxtacrine Mechanism Mediated by P-Selectin Glycoprotein Ligand-11 (2009)
  • Author(s): Kenji Ohba, Akihide Ryo, Zahidunnabi Dewan, Mayuko Nishi, Toshio Naito, Xiaohua Qi, Yoshio Inagaki, Yoji Nagashima, Yuetsu Tanaka, Takashi Okamoto, Kazuo Terashima, Naoki Yamamoto
  • Journal Title: J.Immunol. 183 Pages: 524-532
  • Peer Reviewed
• [Journal Article] Inhibition of the SDF-1α-CXCR4 axis by the CXCR4 antagonist AMD3100 suppresses the migration of cultured cells form ATL patients and murine lymphoblastoid cells from HTLV-I Tax transgenic mice (2009)
  • Author(s): Akira Kawaguchi, Yasuo Orba, Takashi Kimura, Hidekatsu Iha, Masao Ogata, Takahiro Tsuji, Akira Ainai, Tetsutaro Sata, Takashi Okamoto, William W.Hall, Hirofumi Sawa, Hideki Hasegawa
  • Journal Title: Blood 114 Pages: 2961-68
  • Peer Reviewed
• [Journal Article] Cychn T1 stabilizes expression levels of HIV-1 Tat in cells (2009)
  • Author(s): Kenichi Imai, Kaori Asamitsu, Ann Florence B.Victoriano, Marni E.Cueno, Koh Fujinaga
  • Journal Title: FEBS J. 276 Pages: 7124-33
  • Peer Reviewed
• [Journal Article] Inhibition of Inflammatory Cytokine Production from Rheumatoid Synovial Fibroblasts by a Novel IκB Kinase Inhibitor (2009)
  • Author(s): Atsushi Tsuchiya, Kenichi Imai, Kaori Asamitsu, Yuko Waguri-Nagaya, Takanobu Otsuka, Takashi Okamoto
  • Journal Title: JPET 333 Pages: 236-243
  • Peer Reviewed
• [Presentation] Epigenetic Control of the HIV Latent Infection (2011)
  • Author(s): Okamoto T, Victoriano AF, Asamitsu K, Imai K.
  • Organizer: 6th German-Japanese HIV-Symposium
  • Place of Presentation: Bochum(German)
• [Presentation] Involvement of the N-terminal region of human Cyclin T1 for the trans-activation of Human Immunodeficiency Virus-1 transcription by Tat (2011)
  • Author(s): Asamitsu K, and Okamoto T.
  • Organizer: Transcription Elongation in Health and Disease
  • Place of Presentation: Lucca(Italy)
• [Presentation] Epigenetic Control of the HIV Latent Infection (2011)
  • Author(s): Takashi Okamoto, Ann Florence Victoriano, Kaori Asamitsu, Kenichi Imai
  • Organizer: 6^<th> German-Japanese HIV-Symposium
  • Place of Presentation: Bochum (Germany)
• [Presentation] Altered signaling cascade in ATL cell lines : implication for the development of anti-NF-κB therapy in ATL (2011)
  • Author(s): Yurina Hibi, Kaori Asamitsu, Takashi Okamoto
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場・愛知
• [Presentation] Involvement of the N-terminal region of human Cyclin T1 for the trans-activation of Human Immunodeficiency Virus-1 transcription by Tat (2011)
  • Author(s): Kaori Asamitsu, Takashi Okamoto
  • Organizer: Transcription Elongation in Health and Disease
  • Place of Presentation: Lucca (Italy)
• [Presentation] Deciphering microRNA Pathway Interactions of Host and HIV-1 Regulatory and Accessory Genes (2011)
  • Author(s): Neil H Tan Gana, Yurina Hibi, Miyuki Sakai, Ann Florence B Victoriano, Takashi Okamoto
  • Organizer: International Union of Microbiological Societies 2011 Congress
  • Place of Presentation: 札幌コンベンションセンター・北海道
• [Presentation] 関節リウマチモデルマウス(D1CCマウス)における早期間質性肺炎の解析 (2011)
  • Author(s): 金澤智、岡本尚
  • Organizer: 第32回日本炎症・再生医学会
  • Place of Presentation: 国立京都国際会館・京都
• [Presentation] Developing of small molecular weight anti-Tat drug using the predicted 3-D structure of Tat-TAR-cyclinT1 complex. (2010)
  • Author(s): Takashi Okamoto, Yurina Hibi, Ann-Florence Victoriano, Kaori Asamitsu.
  • Organizer: 5th German-Japanese HIV-SYMPOSIUM
  • Place of Presentation: 東京(慶應大学三田キャンパス)
  • Year and Date: 2010-05-10
• [Presentation] Re-evaluating the cause of HIV-1 Tat oxidative stress using plants. (2010)
  • Author(s): Marni E.Cueno, Yurina Hibi, Takashi Okamoto.
  • Organizer: 5th German-Japanese HIV-SYMPOSIUM
  • Place of Presentation: 東京(慶應大学三田キャンパス)
  • Year and Date: 2010-05-10
• [Presentation] Added advantages using plant-based vaccine strategies against AIDS and Influenza : better immunogenisity, more heat-stable and rapid transient protein production. (2010)
  • Author(s): Marni E.Cueno, Haruka Yamato, Yurina Hibi, Takashi Okamoto.
  • Organizer: 14th International Congress of Immmunology.
  • Place of Presentation: 神戸(神戸ポートピアホテル、神戸国際展示場)
• [Presentation] Development of anti-Tat drugs by in silico drug-screening using the predicted 3-D structure of Tat-TAR-cyclin T1 complex. (2010)
  • Author(s): Takashi Okamoto, Yurina Hibi, Kaori Asamitsu
  • Organizer: 12th Annual International Meeting of the Institute of Human Virology.
  • Place of Presentation: Tropea (Italy) (Sunshine Club Hotel White chest snc Loc)
• [Presentation] HIVの転写活性化因子Tatと転写身長因子P-TEFbの相互作用の解析 (2010)
  • Author(s): Kaori Asamitsu, Yurina Hibi, Miyuki Sakai, Takashi Okamoto.
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会
  • Place of Presentation: 神戸(神戸ポートアイランド)
• [Presentation] Computational Prediction of micro RNAs Ptentially Modulating Biomolecular Pathways in host-HIV-1 Interactions. (2010)
  • Author(s): Neil H.Tan Gana, Yurina Hibi, Ann-Florence B.Victoriano, Takashi Okamoto.
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会
  • Place of Presentation: 神戸(神戸ポートアイランド)
• [Presentation] 歯周病原菌の代謝産物・酪酸による潜伏HIV-1プロウイルス活性化の秀子機構 (2009)
  • Author(s): 今井健一, 落合邦康, 岡本尚
  • Organizer: 第52回秋季日本歯周病学会学術大会
  • Place of Presentation: 宮崎観光ホテル(宮崎市)
  • Year and Date: 2009-10-11
• [Presentation] Feasibility of a plant-based vaccine against HIV-1 (2009)
  • Author(s): Marni E Cueno, Yurina Hibi, Katsuo Karamatsu, Yasuhiro Yasutomi, Antonio C.Laurena, Takashi Okamoto
  • Organizer: 4th Semmering Vaccine Symposium 2009
  • Place of Presentation: Vienna, Austria
• [Presentation] Immunization against HIV-1 Tat using a plant system (2009)
  • Author(s): Marni E Cueno, Yurina Hibi, Katsuo Karamatsu, Yasuhiro Yasutomi, Antonio C Laurena, Takashi Okamoto
  • Organizer: 1st International Kishimoto Foundation Symposium, Immune Regulation : Present and Future
  • Place of Presentation: 大阪国際会議場(大阪市)
• [Presentation] 歯周病原細菌による潜伏感染HIV-1の活性化 (2009)
  • Author(s): 今井健一, 岡本尚, 落合邦康
  • Organizer: 日本歯学保存学会2009年度春季学術大会
  • Place of Presentation: 札幌コンベンションセンターSORA(札幌市)
• [Presentation] Plant-based vaccine approach in inducing an immunogenic response against HIV (2009)
  • Author(s): Marni E Cueno, Yurina Hibi, Katsuo Karamatsu, Yasuhiro Yasutomi, Antonio C.Laurena, Takashi Okamoto
  • Organizer: 5th International AIDS symposium
  • Place of Presentation: Cape Town, South Africa
• [Presentation] Potential plant-based HIV-1 Tat vaccine : preferencial expression and immunogenicity (2009)
  • Author(s): Marni E Cueno, Takashi Okamoto
  • Organizer: Vaccine 3rd Global Congress
  • Place of Presentation: Singapore
• [Presentation] Potential of an HIV-1 Tat fusion protein expressed in tomato as a plant-based HIV vaccine (2009)
  • Author(s): Marni E Cueno, Yurina Hibi, Katsuo Karamatsu, Yasuhiro Yasutomi, Antonio C Laurena, Takashi Okamoto
  • Organizer: AIDS Vaccine 2009
  • Place of Presentation: Paris, France
• [Presentation] Histone H3 Lysine 9ジメチル化酵素G9aによる潜伏感染HIVの維持とG9a阻害剤BIX01294によるその破綻機構の解析 (2009)
  • Author(s): 今井健一, 戸上博昭, 岡本尚
  • Organizer: 第57回日本ウイルス学会学術集会
  • Place of Presentation: 都市センターホテル(東京都)
• [Presentation] HIVのTatによるウイルス転写活性化機構の解析 (2009)
  • Author(s): 朝光かおり, 日比悠里名, 小林雄祐, 岡本尚
  • Organizer: 第57回日本ウイルス学会学術集会
  • Place of Presentation: 都市センターホテル(東京都)
• [Presentation] 潜伏感染HIVの維持における Histone H3 Lysine9ジメチル化酵素G9aの役割 (2009)
  • Author(s): 今井健一, 戸上博昭, 岡本尚
  • Organizer: 第23回日本エイズ学会学術集会・総会
  • Place of Presentation: 名古屋国際会議場(名古屋市)
• [Presentation] HIV-1 TatとCyclinT1の相互作用の解析 (2009)
  • Author(s): 朝光かおり, 日比悠里名, 小林雄祐, 岡本尚
  • Organizer: 第23回日本エイズ学会学術集会・総会
  • Place of Presentation: 名古屋国際会議場(名古屋市)
• [Presentation] Histone H3 Lys9 ジメチル化酵素G9a によるHIV-1 転写抑制機構 (2009)
  • Author(s): 戸上博昭, 今井健一, 岡本尚
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜(横浜市)
• [Presentation] Identifi cation of an active ingredient on Inula helenium extracts for NF-κB inhibition (2009)
  • Author(s): 朝光かおり, 石橋貴宏, 田中清隆, 日比悠里名, 小林雄祐, 岡本尚
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜(横浜市)
• [Patent(Industrial Property Rights)] HIV複製阻害剤 (2012)
  • Inventor(s): 岡本尚、朝光かおり、宮田直樹、鈴木孝禎
  • Industrial Property Rights Holder: 岡本尚、朝光かおり、宮田直樹、鈴木孝禎
  • Filing Date: 2012-02-23
  • Overseas
• [Patent(Industrial Property Rights)] HIV複製阻害剤 (2012)
  • Inventor(s): 岡本尚、朝光かおり、宮田直樹、鈴木孝禎
  • Industrial Property Rights Holder: 岡本尚、朝光かおり、宮田直樹、鈴木孝禎
  • Filing Date: 2012-02-23
• [Patent(Industrial Property Rights)] HIV複製阻害剤 (2012)
  • Inventor(s): 岡本尚、朝光かおり、宮田直樹、鈴木孝禎
  • Industrial Property Rights Holder: 岡本尚、朝光かおり、宮田直樹、鈴木孝禎
  • Filing Date: 2012-02-23
  • Overseas
• [Patent(Industrial Property Rights)] HIV増殖抑制剤 (2009)
  • Inventor(s): 岡本尚, 朝光かおり, 日比悠里名
  • Industrial Property Rights Holder: 名古屋市立大学
  • Industrial Property Number: 2009-254740
  • Filing Date: 2009-11-06