Research of inhibitors for nuclear transport or enzyme activity of protein kinases encoded by human herpesviruses

• Project/Area Number: 20611009
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Chemical biology
• Research Institution: Osaka University
• Principal Investigator: ISEGAWA Yuji Osaka University, 医学系研究科, 准教授 (20184583)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: ヘルペスウイルス / GCV耐性ウイルス / 蛋白キナーゼ / 核輸送 / 検査法 / 阻害剤 / HHV-6 / DNAポリメラーゼ

Research Abstract

Human herpesvirus 6 (HHV-6) ganciclovir-resistant strain was obtained with amino acid substitutions associated with the death of a recipient after an allogeneic stem cell transplant recipient. The substitutions on U38 DNA polymerase of HHV-6 were associated with the ganciclovir-resistance of HHV-6. The assays to detect antiviral drug-resistance mutations of HHV-6 were developed. The assay has been developing the powerful detection system which is rapid and multi-screening method. The nuclear transport mechanism of U69 protein was cleared, and it is started that the multi-screening assay system is been developing to detect the inhibitors for the nuclear transport.

Research Products

• [Journal Article] PCR with quenching probes enables the rapid detection and identfication of ganciclovir-resistance-causing U69 gene mutations in human herpesvirus 6. (2010)
  • Author(s): Y.Isegawa, C.Matsumoto, K.Nishinaka, K.Nakano, T.Tanaka, N.Sugimoto, A.Ohshima
  • Journal Title: Molecular and Cellular Probes 24 Pages: 167-177
  • Peer Reviewed
• [Journal Article] PCR with quenching probes enables the rapid detection and identfication of ganciclovir-resistance-causing U69 gene mutations in human herpesvirus 6. (2010)
  • Author(s): Y.Isegawa, C.Matsumoto, K.Nishinaka, K.Nakano, T.Tanaka, N.Sugimoto, A.Ohshima
  • Journal Title: Molecular and Cellular Probes Volume: 24 Pages: 167-177
  • Peer Reviewed
• [Journal Article] PCR with quenching probes enables the rapid detection and identification of ganciclovir-resistant causing U69 gene mutations in human herpesvirus 6 (2010)
  • Author(s): Y.Isegawa, C.Matsumoto, K.Nishinaka, K.Nakano, T.Tanaka, N.Sugimoto.A.Ohshima
  • Journal Title: Molecular and Cellular Probes 24(In press)
  • Peer Reviewed
• [Journal Article] Detection and identification of U69 gene mutations encoded by ganciclovir-resistant human herpesvirus 6 using denaturing high-performance liquid chromatography. (2009)
  • Author(s): K.Nakano, K.Nishinaka, T.Tanaka, A.Ohshima, N.Sugimoto, Y.Isegawa
  • Journal Title: Journal of Virological Methods 161 Pages: 223-230
  • Peer Reviewed
• [Journal Article] Relationship between U83 gene variation in human herpesvirus 6 and secretion of the U83 gene product. (2009)
  • Author(s): R.Sjahril, Y.Isegawa, T.Tanaka, K.Nakano, T.Yoshikawa, Y.Asano, A.Ohshima, K.Yamanishi, N.Sugimoto
  • Journal Title: Archives of Virology 154 Pages: 273-283
  • Peer Reviewed
• [Journal Article] Human herpesvirus 6 ganciclovir-resistant strain with amino acid substitutions associated with the death of a recipient after an allogeneic stem cell transplant recipient. (2009)
  • Author(s): Y.Isegawa J.Hara, K.Amo, Y.Osugi, M.Takemoto, K.Yamanishi, R.Fukunaga, M.Shibata, A.Ohshima, Y.Horiguchi, N.Sugimoto
  • Journal Title: Journal of Clinical Virology 44 Pages: 15-19
  • Peer Reviewed
• [Journal Article] Relationship between U83 gene variation in humen herpesvirus 6 and secretion of the U83 gene product (2009)
  • Author(s): R.Sjahril, Y.Isegawa, T.Tanaka, K.Nakano, T.Yoshikawa, Y.Asano, A.Ohshima, K.Yamanishi, N.Sugimoto
  • Journal Title: Archives of Virology 154 Pages: 273-283
  • Peer Reviewed
• [Journal Article] Detection and identification of U69 gene mutations encoded by ganciclovir-resistant human herpesvirus 6 using denaturing high-performance liquid chromatography (2009)
  • Author(s): K.Nakano, K.Nishinaka, T.Tanaka, A.Ohshima, N.Sugimoto, Y.Isegawa
  • Journal Title: Journal of Virological Methods 161 Pages: 223-230
  • Peer Reviewed
• [Journal Article] Human herpesvirus 6 ganciclovir-resistant strain with amino acid substitutions associated with filedeath of a recipient after an allogeneic stem cell transplant recipient (2009)
  • Author(s): Y. Iseeawa, J. Hara, K. Amo, Y. Osugi, M. Takanoto, K. Yamanishi, R. Fukunaga, M. Shibata, A. Ohshima, Y. Horiguchi, N. Sugimoto
  • Journal Title: Journal of Clinical Virology 44 Pages: 15-19
  • Peer Reviewed
• [Presentation] ヒトヘルペスウイルス6のガンシクロビル耐性変異株のQP-PCRを用いた迅速検出法の開発 (2009)
  • Author(s): 伊勢川裕二、松本智紗, 西中和子、中野和司、大島淳、杉本央
  • Organizer: 日本細菌学会関西支部会総会
  • Place of Presentation: 大阪府立大学りんくうキャンパス
  • Year and Date: 2009-11-14
• [Presentation] HHV-6 U69の核移行シグナルの機能解析 (2009)
  • Author(s): 中野和司、安田善也、伊勢川裕二
  • Organizer: 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
  • Year and Date: 2009-10-26
• [Presentation] HHV-6 U69の核移行シグナルの機能解析 (2009)
  • Author(s): 中野和司, 安田善也, 伊勢川裕二
  • Organizer: 日本ウイルス学会学術集会
  • Place of Presentation: 都市センターホテル
  • Year and Date: 2009-10-26
• [Presentation] U83 gene Variations Among Human Herpesvirus 6 from Exanthem Subitum patients, Transplant Recipients, and Healthy Donors. (2008)
  • Author(s): R.Sjahril, Y.Isegawa, T.Tanaka, K.Nakano, T.Yoshikawa, Y.Asano, A.Ohshima, K.Yamanishi, N.Sugimoto
  • Organizer: 日本ウイルス学会術集会
  • Place of Presentation: 剛山コンベンションセンター
  • Year and Date: 2008-10-27
• [Presentation] dHPLCを用いたガンシクロビル耐性HHV-6 U69遺伝子の変異検出法の確立 (2008)
  • Author(s): 中野和司、西中和子、大島淳、伊勢川裕二
  • Organizer: 日本ウイルス学会学術集会
  • Place of Presentation: 岡山コンベンションセンター
  • Year and Date: 2008-10-27
• [Presentation] Allogeneicstem cell移植患児の死に関連したHHV-6ガンシクビル耐性株のアミノ酸置換 (2008)
  • Author(s): 伊勢川裕二、天羽清子、武本眞清、山西弘一, 柴田真理、大島淳
  • Organizer: 日本ウイルス学会学術集会
  • Place of Presentation: 岡山コンベンションセンター
  • Year and Date: 2008-10-27
• [Presentation] Allogeneic stem cell 移植患児の死に関連したHHV-6ガンシクビル耐性株のアミノ酸置換 (2008)
  • Author(s): 伊勢川裕二, 天羽清子, 武本眞青, 山西弘一, 柴田真理, 大島淳
  • Organizer: 日本ウイルス学会学術集会
  • Place of Presentation: 岡山コンベンションセンター
  • Year and Date: 2008-10-27